Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
 ...
PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76

Using a selective immunochemical method, the activities of postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were measured in 7 children with newly diagnosed IDDM, 39 on a conventional subcutaneous insulin regimen (CSC), and 11 children receiving continuous subcutaneous infusion of insulin (CSII). The newly diagnosed untreated patients frequently had hypertriglyceridemia and a decreased serum HDL-cholesterol level, while they showed a mild, but not significant increase of the serum total cholesterol level. The insulin-treated patients (both on CSC and on CSII) had serum lipid levels similar to those in controls. LPL activity was decreased in untreated patients, and insulin treatment resulted in an increase in the LPL activity with a concomitant normalization of serum triglyceride and HDL-cholesterol levels. In contrast to the patients on CSII who had normal LPL activity, patients on CSC had an increased LPL activity. This may have been due to peripheral hyperinsulinemia. HTGL activity did not show any increase during the time of improved diabetic control. In conclusion; (1) serum lipid levels were normal both in the patients on CSC and CSII. (2) LPL activity was normal on CSII, but was increased on CSC and decreased in untreated patients.
 ...
PMID:Serum lipids and postheparin plasma lipase activity in Japanese children with ketosis-prone diabetes mellitus. 644 Mar 12

In IDDM patients, serum high-density lipoprotein cholesterol concentrations have been reported to be normal or elevated. The spectrum of high-density lipoprotein particles is highly heterogeneous, but no data are available on the subpopulations of high-density lipoprotein in IDDM. We, therefore, studied the spectrum of high-density lipoprotein particles in 86 IDDM patients (51 men and 35 women) 37 +/- 10 yr of age and in 74 sex-, age-, and body mass index-matched healthy nondiabetic subjects. The concentrations of high-density lipoprotein and HDL2 cholesterol were higher in the IDDM group than in the control subjects (P < 0.01). The apoA-I-to-apoA-II ratio was higher in the IDDM patients than in the nondiabetic subjects (P < 0.001) because of an increased concentration of LpA-I particles (61 +/- 17 vs. 53 +/- 15, P < 0.01). LpA-I particles correlated positively with high-density lipoprotein and HDL2 cholesterol in the two groups. Postheparin plasma lipoprotein lipase activity was significantly higher in the IDDM group than in the control group (P < 0.001), whereas postheparin plasma hepatic lipase activities were similar in both groups. Plasma cholesteryl ester transfer protein activity was estimated in an in vitro isotopic assay using exogenous labeled donor (low-density) and acceptor (high-density) lipoproteins in the absence of native lipoproteins. We observed no difference in cholesteryl ester transfer protein activity between the groups, and no significant correlations existed between cholesteryl ester transfer protein activity and high-density lipoprotein subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of apolipoprotein A-I-containing lipoproteins in IDDM. 834 39

Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c > 8%, n = 18) or good blood glucose control (group 2, HbA1c < 8%, n = 16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175-400; intermediate, Sf 100-175; small, Sf 20-100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49 +/- 2%; p < 0.005; group 2: 51 +/- 3%, p < 0.01; control subjects 40 +/- 2%) (mean +/- SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35 +/- 4 vs 27 +/- 3 mg/dl, p = 0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254 +/- 19 mU/ml, p < 0.05; group 2: 202 +/- 19 mU/ml, p < 0.005; control subjects 317 +/- 31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.
 ...
PMID:Very low density lipoprotein subfraction abnormalities in IDDM patients: any effect of blood glucose control? 878 15

Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.
 ...
PMID:Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM. 903 97

Type 1 diabetes is associated with coronary heart disease (CHD) and coronary artery calcification (CAC), a measure of subclinical CHD. The hepatic lipase gene promoter polymorphism (LIPC-480C>T) is a common variant affecting lipid metabolism. This study examined the relation between the LIPC-480C>T and CAC in type 1 diabetes. In the type 1 diabetic patients studied, 56% had CAC >0 Agatston units (AU). These subjects had a longer duration of diabetes (26.2 +/- 1.3 vs. 17.8 +/- 1.4 years; P < 0.001), lower HDL cholesterol levels (55.7 +/- 2.4 vs. 61.0 +/- 2.5 mg/dl; P = 0.05), higher triglyceride levels (101 +/- 17.3 vs. 66 +/- 7.6 mg/dl; P < 0.05), and higher diastolic blood pressure (79.7 +/- 1.0 vs. 76.0 +/- 1.4 mmHg; P < 0.05). The LIPC-480 T allele was more common in subjects with CAC (frequency = 0.31 +/- 0.05 vs. 0.14 +/- 0.04; P = 0.006). The proportion with CAC was 44% in LIPC-480CC subjects, 71% in heterozygotes, and 83% in LIPC-480TT subjects (P < 0.01). LIPC-480 T allele frequency increased as the amount of CAC increased (P = 0.007). LIPC-480 genotype was independently associated with the CAC (odds ratio = 2.90, 95% CI 1.22-6.92, P < 0.05) after adjusting for duration of diabetes, age, sex, diastolic blood pressure, HDL cholesterol, and triglyceride levels. In conclusion, the LIPC-480C>T polymorphism was associated with subclinical CHD in type 1 diabetes. This genetic variant may identify subjects in which early intervention to prevent CHD may be appropriate.
 ...
PMID:A common promoter polymorphism in the hepatic lipase gene (LIPC-480C>T) is associated with an increase in coronary calcification in type 1 diabetes. 1191 46

Excessive weight gain in a subset of intensively treated Diabetes Control and Complications Trial (DCCT) subjects was associated with higher waist to hip ratio; higher triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (ApoB) in the presence of small-dense LDL; and decreased high-density lipoprotein 2 cholesterol (HDL2-C), suggesting that weight gain in these subjects resulted in higher intraabdominal fat (IAF), and an atherosclerotic dyslipidemia mediated through hepatic lipase activity (HL). Objectives were to investigate relationships between IAF, HL, and dyslipidemia and to relate IAF to previous body mass index change during the DCCT. Sixty-one subjects were studied approximately 4 yr after DCCT closeout. IAF was positively related to HL (P < 0.001). IAF positively correlated with logTG (P < 0.001) and ApoB (P < 0.001), and negatively with LDL relative flotation rate (P < 0.001) and logHDL2-C (P = 0.001). HL accounted for most of the relationship between IAF with logHDL2-C and LDL relative flotation rate, and none of the relationship between IAF and logTG or ApoB. DCCT-related body mass index change accounted for a significant portion of logIAF variance measured 4 yr later (P < 0.001). Elevated IAF in subjects with type 1 diabetes was related to an atherosclerotic dyslipidemia similar to that seen in individuals without diabetes who have metabolic syndrome. DCCT-related weight gain positively correlated with subsequent IAF.
 ...
PMID:Visceral obesity, hepatic lipase activity, and dyslipidemia in type 1 diabetes. 1284 91