Lipids, lipoproteins and apolipoprotein (a) isoforms in type 2 diabetic patients.

BACKGROUND: Patients with type 2 diabetes mellitus have a greater than normal risk of developing atherosclerotic vascular diseases. Higher than normal plasma concentrations of lipoprotein (a) [Lp(a)] have been associated with premature atherosclerosis in several studies. OBJECTIVE: To determine the concentrations of lipids, lipoproteins, and Lp(a) in 107 type 2 diabetic patients, and the distribution of apolipoprotein (a) [apo(a)] phenotypes for this group, and to compare the results found with results for healthy subjects. RESULTS: Plasma concentrations of cholesterol, triglycerides, and apolipoprotein B in the diabetics were significantly higher than those in control subjects. Diabetic patients had slightly lower Lp(a) concentrations than did nondiabetic subjects, but these differences were not statistically significant. Distributions of Lp(a) concentrations both in type 2 diabetic patients and in control subjects were markedly skewed, the highest prevalences being of low values. CONCLUSION: Distributions of apo(a) phenotypes for patients with type 2 diabetes mellitus and controls were remarkably alike. Smaller isoforms were similarly prevalent for the two populations, as were the null, single-band and double-band apo(a) phenotypes.     

Plasma lipoprotein (a) levels in Turkish NIDDM patients with and without vascular diabetic complications.

OBJECTIVE: Plasma concentrations of lipoprotein (a) [Lp(a)], an independent risk factor for atherosclerosis, were measured in 59 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without vascular complications, and 21 non-diabetic healthy subjects. RESULTS: The plasma log Lp(a) levels were found to be significantly increased in the NIDDM patients (1.40 +/- 0.36) compared with the healthy subjects (1.02 +/- 0.53; p < 0.05). Plasma Lp(a) levels in NIDDM patients with diabetic vascular complications (1.51 +/- 0.27) were significantly higher than those of the NIDDM patients without diabetic vascular complications (1.23 +/- 0.43) and healthy subjects (p < 0.05). There were significant correlations between plasma log Lp(a) levels and apolipoprotein B (apo B) in all NIDDM patients (r: 0.68, p < 0.05). No correlation was observed between Lp(a) levels and age, sex, duration of diabetes, fasting blood glucose, haemoglobin Alc, the mode of treatment, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein Al levels in all patients. CONCLUSIONS: It was concluded that Lp(a) was a risk factor for angiopathy in NIDDM patients and the patients who have a high plasma Lp(a) concentration should be kept under strict glycaemic control.     

Predictive value of lipoprotein (a) and other serum lipoproteins in the angiographic diagnosis of coronary artery disease

To determine the relation among lipids in predicting coronary artery disease (CAD), 213 patients undergoing diagnostic angiography for suspected CAD were prospectively studied. Twenty-one patients had normal coronary arteries and 192 had CAD in 1 to 3 arteries at arteriography with measurements obtained with digital calipers. Lipoproteins were measured and lipoprotein (a) [Lp(a)] was also assayed in a subset of 98 patients with CAD. Statistical analysis was performed using uni- and multivariate techniques to test the association among age, gender, systemic hypertension, diabetes mellitus, cigarette smoking, family history, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein cholesterol, apolipoproteins (apo) A-I and apo B, ratio of apo A-I to apo B, and ratio of HDL cholesterol to total cholesterol, to Lp(a) and to CAD. All factors except gender, systemic hypertension, diabetes mellitus and cigarette smoking were univariate predictors of CAD. Multivariate predictors were, in decreasing order of significance, family history, age, HDL/total cholesterol ratio and apo B. When Lp(a) was included, multivariate predictors were age, family history, apo B and Lp(a), in that order. Lipid parameters alone showed that the HDL/total cholesterol ratio and that Lp(a) provide the best predictive tests for the detection of CAD in this referral population and may ultimately become important screening tests for CAD.     

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.     

Lipids and lipoprotein(a) concentrations in Pakistani patients with type 2 diabetes mellitus

AIM: The aim of the present study was to analyze serum lipoprotein(a) [Lp(a)] levels in Pakistani patients with type 2 diabetes mellitus (DM) and to find correlations between clinical characteristics and dyslipidaemias in these patients. METHODS: Fasting blood samples were analyzed for Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose and glycosylated haemoglobin (HbA1c) in 68 Pakistani patients with type 2 DM and 40 non-diabetic healthy control subjects. RESULTS: Lp(a) levels were significantly raised in diabetics as compared to the control group. No correlation of Lp(a) was seen with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. There was a positive correlation of BMI to SBP and DBP. There was a significant positive correlation between Lp(a) and total cholesterol and LDL-c. No correlation of Lp(a) was observed with HDL-c, triglycerides and glycosylated haemoglobin (HbA1c). CONCLUSION: The present study led us to conclude that serum Lp(a) levels are significantly raised in type 2 DM and have a positive correlation with serum total and LDL-c levels.     

Plasma lipoprotein(a) concentration and phenotypes in diabetes mellitus

Summary Patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are at increased risk of developing atherosclerotic vascular diseases. A variety of lipoprotein abnormalities have been described as being associated with this increased risk. In this study, apo(a) isoform frequencies and lipoprotein(a) [Lp(a)] concentrations were determined in Type 1 and Type 2 diabetic patients in order to investigate a possible contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. No significant differences in plasma Lp(a) concentrations were found in two ethnically different populations (Austrians from the province of Tyrol and Hungarians from Budapest) in either type of diabetes when compared to respective control groups (91 Type 1 and 112 Type 2 diabetic patients vs 202 control subjects in the Hungarian study and 44 Type 1 diabetic and 44 Type 2 diabetic vs 125 control subjects in the Austrian study). There were also no significant apo(a) isoform frequency differences between both patient groups and control subjects in the two study groups. These data, obtained from two large ethnically different populations, provide no evidence of a contribution of Lp(a) to the increased risk for atherosclerosis in diabetes.     

Adiponectin is independently associated with apolipoprotein B to A-1 ratio in Koreans

Apolipoprotein B to A-1 (apo B/A-1) ratio is reportedly a better predictor of atherosclerotic vascular disease than low-density lipoprotein cholesterol (LDL-C). The aim of this study was to assess the association of serum apo B/A-1 ratio with insulin resistance and adiponectin in patients with different grades of glucose intolerance. Patients were divided according to glucose tolerance into 3 groups: normal glucose tolerance without metabolic syndrome (n = 229), impaired fasting glucose (subjects with fasting plasma glucose level between 100 and 125 mg/dL, n = 658), and type 2 diabetes mellitus (n = 381). Serum concentrations of apo B, apo A-1, glucose, total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance index (HOMA-IR). There were significant differences in metabolic parameters among the groups, including waist circumference, insulin, HOMA-IR, and apo B/A-1 ratio, which increased sequentially with glucose intolerance, whereas adiponectin level decreased with increasing severity of glucose intolerance. The apo B/A-1 ratio was significantly correlated with TC, triglycerides, LDL-C, HDL-C, adiponectin, and HOMA-IR in normal glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus. Multiple regression analysis showed that apo B/A-1 ratio was significantly associated with TC, LDL-C, HDL-C, and adiponectin. In conclusion, apo B/A-1 ratio was significantly associated with insulin resistance according to glucose intolerance; and serum adiponectin was an important independent factor associated with apo B/A-1 ratio in Koreans.     

Relation of lipoprotein(a) as coronary risk factor to type 2 diabetes mellitus and low-density lipoprotein cholesterol in patients > or =65 years of age (The Italian Longitudinal Study on Aging)

High levels of serum lipoprotein(a) [Lp(a)] have been associated with increased risk of coronary artery disease (CAD), but this association apparently is not confirmed in elderly people. We evaluated the interactions of Lp(a) with lipid and nonlipid CAD risk factors in a sample of subjects enrolled in the prevalence survey (1992 to 1993) of the Italian Longitudinal Study on Aging (ILSA). The entire population consisted of 5,632 elderly people, aged 65 to 84 years, randomly selected in 8 Italian municipalities. The present cross-sectional study included 400 free-living elderly subjects (74 +/- 6 years) from the randomized cohort of Casamassima (Bari, Southern Italy) (n = 704). The results showed that in the elderly population, high serum Lp(a) is a CAD risk factor dependent on type 2 diabetes mellitus and elevated low-density lipoprotein (LDL) cholesterol levels. In particular, the combined effect of high Lp(a) (> or =20 mg/dl) and high LDL cholesterol (> or =3.63 mmol/L [> or =140 mg/dl]), increases coronary risk by 2.75 (95% confidence interval 7.70 to 0.99); finally, the effect of Lp(a) > or =20 mg/dl and LDL cholesterol > or =3.63 mmol/L (> or =140 mg/dl), combined with type 2 diabetes mellitus, increases risk of CAD by 6.65 (95% confidence interval 35.40 to 1.25). In the elderly, elevated Lp(a) levels appear not to be an independent predictor of CAD, but this lipoprotein is a risk factor only in subjects with type 2 diabetes mellitus and elevated LDL cholesterol.     

Hyperinsulinemia, lipoprotein (a), and Chlamydia pneumoniae antibodies--are they risk factors or serologic predictors for progression of coronary artery disease?

The authors studied 134 patients with unstable angina pectoris symptoms and 32 subjects without coronary artery disease (CAD) for the presence of classical risk factors such as hypercholesterolemia, smoking, and family history of CAD. In addition they analyzed plasma insulin levels, lipoprotein (a) (Lp [a]) levels, and antibody titers against Chlamydia pneumoniae. All patients had a heart catheterization. Patients with diabetes mellitus were excluded from the study. Fasting insulin, low-density lipoprotein (LDL) cholesterol and Chlamydia pneumoniae immunoglobulin G (IgG) and IgA antibody titers did not show any difference in CAD from healthy control subjects, whereas Lp(a) was increased and high-density lipoprotein (HDL) decreased in CAD patients. These data indicate that lipoprotein (a), low HDL cholesterol, and smoking, but neither hyperinsulinemia nor elevated Chlamydia pneumoniae titers, are risk factors or predictors for CAD.     

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276±78 vs 149±46 units/l). Type 2 diabetic patients had considerably higher levels of apo (a) than matched controls (471±89 vs 221±61 units/l,P=0.06), though the difference was not statistically significant. However, concentrations of apo (a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.     

2型糖尿病患者血清脂蛋白(a)水平及其与冠心病的关系

目的　探讨 2型糖尿病患者血清脂蛋白 (a) [Lp(a) ]水平及其与冠心病的关系。方法　选择 90例 2型糖尿病及 6 8例健康对照者测定其血清Lp(a)、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)水平 ;计算低密度脂蛋白胆固醇 (LDL C)水平及TC、TG、LDL C与HDL C比值。结果　 (1)糖尿病组血清Lp(a)水平与对照组比较差异无显著性意义 (P >0 .0 5 )。 (2 )将 2型糖尿病患者分为糖尿病伴冠心病和单纯糖尿病亚组后发现 :①糖尿病伴冠心病亚组血清Lp(a)水平明显高于单纯糖尿病亚组 [(2 3.78± 2 3.73)mg/dlvs (13.31± 10 .6 6 )mg/dl;P <0 .0 1]及对照组 [(2 3.78± 2 3.73)mg/dlvs (16 .2 8± 17.95 )mg/dl;P <0 .0 5 ];②糖尿病伴冠心病亚组血清Lp(a)水平与LDL C呈正相关关系 (r =0 .32 16 ,P <0 .0 5 )。结论　 2型糖尿病患者血清Lp(a)水平增高可能与冠心病发病有密切关系。     

The lipid triad in type 2 diabetes - prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes.

Cardiovascular disease is the major cause of morbidity and mortality in type 2 diabetes mellitus. Among the established risk factors, the lipid triad (elevated triglycerides, decreased high-density lipoprotein cholesterol, and small dense low-density lipoprotein cholesterol) is a powerful risk factor for atherosclerosis in type 2 diabetes. The prevalence of hypertriglyceridaemia (HTG) in type 2 diabetes is two to three times higher than in non-diabetics. The Copenhagen Male study, the AMORIS study, and several other trials showed hypertriglyceridaemia to be an independent predictor of coronary heart disease (CHD). HTG may promote risk both directly and indirectly through association with alterations of lipoprotein size and composition. The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) demonstrated that raising high-density lipoprotein cholesterol (HDL-C) in patients with low (HDL-C) and low-density lipoprotein cholesterol (LDL-C) is associated with a significant reduction in CHD risk. It was shown in the Diabetes Intervention Study, AFCAPS/TexCAPS, and PROCAM studies that decreased HDL-C and elevated triglycerides are independent risk factors for atherosclerosis, particularly in patients with diabetes mellitus. Several epidemiological studies demonstrated that total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratios or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratios could be better predictors of atherosclerosis than any single lipid parameter. Intima-media thickness (IMT), a well established marker of early atherosclerosis, is associated with HTG/low HDL-cholesterol. In the Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study total and HDL-cholesterol were independent determinants of IMT in subjects at risk for type 2 diabetes. Postprandial HTG was also shown to be correlated with increased IMT in type 2 diabetic patients.     

HMG CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels

Lp(a) is a plasma lipoprotein particle consisting of a plasminogenlike protein [apo(a)] disulfide bonded to the apo B moiety of low-density lipoprotein (LDL). Increased plasma levels of Lp(a), either independently or interactively with LDL levels, have been shown to be a risk factor for atherosclerosis. Recently, a new class of lipid-lowering drugs, HMG CoA reductase inhibitors, have been introduced. These drugs act by decreasing liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels. In this study, we examined the effect of HMG CoA reductase inhibitors on Lp(a) levels in three groups of subjects, five volunteers and two groups of five and 14 patients. In all 24 subjects, mean decreases were observed in total cholesterol (43 +/- 5%), total triglyceride (35 +/- 8%), very low-density lipoprotein (45 +/- 9%), and LDL cholesterol (43 +/- 5%). The mean change in high-density lipoprotein cholesterol was an increase of 7 +/- 8%. Despite the very significant decrease in LDL cholesterol levels (p less than 0.001), Lp(a) levels increased by 33 +/- 12% (p less than 0.005). This was not associated with a measurable change in the chemical composition or size of the Lp(a) particle. This emphatically suggests that Lp(a) particles, despite consisting principally of LDL, are cleared from plasma differently than LDL. The surprising finding of an increase in Lp(a) levels suggests this class of drugs may have a direct effect on Lp(a) synthesis or clearance independent of its effect on LDL receptors.     

The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension. An open-label observational study

Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P<.05) and CRP levels (0.33 [0.07-2.05] to 0.25 [0.05-1.84] mg/dL, P<.05) vs baseline. Homocysteine levels were not affected but plasma fibrinogen presented a significant increase (303.5+/-75.1 to 387.5+/-70.4 mg/dL, P<.01) with rosiglitazone. Although no significant changes were observed in the rosiglitazone group for triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol, both apo A-I and apo B presented small significant reductions and the LDL-apo B ratio was significantly increased. None of the above parameters were changed in the control group. In conclusion, rosiglitazone treatment had a beneficial impact on Lp(a), CRP, and LDL particles' lipid content in type 2 diabetic hypertensive patients but not on homocysteine and fibrinogen. The overall effect of rosiglitazone on cardiovascular risk factors seems positive but must be further evaluated.     

Almond consumption improved glycemic control and lipid profiles in patients with type 2 diabetes mellitus

Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-week randomized crossover clinical trial was that almond consumption would improve glycemic control and decrease the risk for cardiovascular disease in 20 Chinese patients with type 2 diabetes mellitus (T2DM) (9 male, 11 female; 58 years old; body mass index, 26 kg/m²) with mild hyperlipidemia. After a 2-week run-in period, patients were assigned to either a control National Cholesterol Education Program step II diet (control diet) or an almond diet for 4 weeks, with a 2-week washout period between alternative diets. Almonds were added to the control diet to replace 20% of total daily calorie intake. Addition of approximately 60 g almonds per day increased dietary intakes of fiber, magnesium, polyunsaturated fatty acid, monounsaturated fatty acid, and vitamin E. Body fat determined with bioelectrical impedance analysis was significantly lower in patients consuming almonds (almonds vs control: 29.6% vs 30.4%). The almond diet enhanced plasma α-tocopherol level by a median 26.8% (95% confidence intervals, 15.1-36.6) compared with control diet. Furthermore, almond intake decreased total cholesterol, low-density lipoprotein cholesterol, and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol by 6.0% (1.6-9.4), 11.6% (2.8-19.1), and 9.7% (0.3-20.9), respectively. Plasma apolipoprotein (apo) B levels, apo B/apo A-1 ratio, and nonesterified fatty acid also decreased significantly by 15.6% (5.1-25.4), 17.4% (2.8-19.9), and 5.5% (3.0-14.4), respectively. Compared with subjects in the control diet, those in the almond diet had 4.1% (0.9-12.5), 0.8% (0.4-6.3), and 9.2% (4.4-13.2) lower levels of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance index, respectively. Our results suggested that incorporation of almonds into a healthy diet has beneficial effects on adiposity, glycemic control, and the lipid profile, thereby potentially decreasing the risk for cardiovascular disease in patients with type 2 diabetes mellitus.     

Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA_1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a) Lipoprotein(a) - apo(a) apolipoprotein(a) - NIDDM non-insulin-dependent diabetes mellitus - TC total cholesterol - LDL low density lipoprotein - TG triglycerides - HDL-C high density lipoprotein-cholesterol - LDL-C low density lipoprotein-cholesterol - PBS phosphate buffered saline The first two authors contributed equally to this work     

Concomitant insulin and sulfonylurea therapy in patients with type II diabetes. Effects on glucoregulation and lipid metabolism

Recent evidence suggests concomitant insulin and sulfonylurea therapy has a theoretical potential in the management of type II diabetes mellitus. In a long-term double-blind, randomized placebo-controlled study of combination therapy, serum glucose, C-peptide, total cholesterol, triglyceride, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations were evaluated in insulin-treated patients with poorly controlled, type II diabetes mellitus after addition of either glyburide (n = 10) or placebo (n = 12). Oral glucose tolerance testing was performed at weeks 0, 4, and 16. Clinical characteristics and glycemic control (fasting blood glucose and glycosylated hemoglobin values) were similar at week 0 in both groups. The placebo group had no change in any metabolic parameter throughout the study period. At week 4, glyburide significantly lowered fasting blood glucose and integrated glucose areas (p less than 0.01) compared with values at week 0 (fasting blood glucose 225 +/- 20 versus 286 +/- 27 mg/dl, p less than 0.02). Mean fasting, stimulated, and integrated C-peptide levels were significantly higher (p less than 0.02) at week 4 versus week 0. At week 16, mean fasting blood glucose values remained significantly lower compared with baseline values (252 +/- 25 versus 286 +/- 27 mg/dl, p less than 0.05). Glycosylated hemoglobin levels decreased significantly (p less than 0.05) at weeks 4 to 16 compared with the baseline values. Although glucose responses and integrated areas were no different after oral glucose tolerance testing, fasting and stimulated C-peptide levels were significantly higher (p less than 0.05) at week 16 versus week 0. Lipid and lipoprotein levels remained unchanged. In summary, combination therapy consisting of glyburide and insulin moderately improved glucose control in type II diabetes mellitus at the end of four weeks. Despite significantly lower fasting serum glucose and glycosylated hemoglobin levels after 16 weeks, combination treatment did not normalize glycemic control. Glucose tolerance decreased further after 16 weeks despite persistence of increased endogenous insulin secretion. The role of the combination therapy in the long-term care of patients with type II diabetes mellitus needs further investigation.     

Hepatic steatosis associated with heterozygotic familial hypobetalipoproteinemia

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.     

The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial

BACKGROUND: Postmenopausal women with diabetes are at high risk for cardiovascular disease, compared with their nondiabetic counterparts. Combined continuous hormone replacement therapy (HRT) is associated with improvements in serum lipoprotein levels in nondiabetic women; however, the effect in women with diabetes has not been determined. We evaluated the effect of combined continuous HRT on lipoprotein and coagulation factor concentrations and glycemic control in postmenopausal women with type 2 diabetes mellitus. METHODS: In a randomized controlled crossover study, 61 subjects received combined continuous HRT or placebo. Each treatment phase was of 6 months' duration, with an 8-week washout phase between treatment phases. RESULTS: Total cholesterol concentration decreased by 7% (95% confidence interval [CI], 4%-11%) during HRT. For low-density lipoprotein concentration, the mean decrease with HRT was 12% (95% CI, 6%-17%). Apolipoprotein B levels decreased in keeping with the reduction in low-density lipoprotein cholesterol concentrations. There were no significant changes in concentrations of high-density lipoprotein, its subfractions, or triglycerides. Lipoprotein(a) and fibrinogen concentrations were reduced by 21% (95% CI, 10%-31%) and 8% (95% CI, 2%-13%), respectively, with HRT. Fructosamine concentrations declined by 5% (95% CI, 2%-9%) during HRT. CONCLUSIONS: In postmenopausal women with type 2 diabetes mellitus, combined continuous HRT has beneficial effects on lipoprotein concentrations and improves some markers of coagulation and glycemic control.     

Lipoprotein(a) concentrations in patients with type 2 diabetes mellitus without cardiovascular disease: relationship to metabolic parameters and diabetic complications

BACKGROUND AND AIM: Diabetes mellitus is associated with a 3-4 times greater risk of coronary artery disease. One of the major risk factors in diabetics is their abnormal plasma lipid and lipoprotein levels, and a high serum concentration of lipoprotein(a) [Lp(a)] is an acknowledged risk factor for atherosclerosis. The aim of this study was to evaluate serum Lp(a) levels in type 2 diabetic (T2DM) patients without cardiovascular disease, and assess the relationship between these levels and microvascular complications. METHODS AND RESULTS: The study involved 86 T2DM patients without cardiovascular disease and 44 healthy control subjects. There were no statistically significant differences between the two groups in terms of mean age, body mass index, total cholesterol, low density lipoprotein-cholesterol or Lp(a) levels. There was a positive correlation between Lp(a) levels and diabetic proliferative retinopathy. Microalbuminuria and serum Lp(a) concentrations were significantly higher in the T2DM patients with proliferative retinopathy, who also had a longer duration of diabetes. CONCLUSIONS: Diabetes does not increase serum Lp(a) concentrations. T2DM patients with high Lp(a) levels may be at high risk of retinopathy.