Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mixed metabolic alkalosis and metabolic acidosis, resulting in an alkalemic state, occurred in a hyperlipemic patient with previously diagnosed non insulin dependent diabetes. The metabolic alkalosis, due to large loss of gastric HCl, was more severe than the diabetic acidosis and resulted in an alkaline blood pH. Initially the metabolic acidosis was due to ketoacidosis and coexistent lactic acidosis. During the improvement of the alkalemic and hyperglycemic state, lactic acidosis disappeared but a paradoxical rise of plasma NEFA and ketone body concentrations supervened so that the high anion gap metabolic acidosis was virtually unchanged. The rise of plasma NEFA was probably related to the marked removal of plasma triglycerides, by insulin activation of lipoprotein lipase, and consequent saturation of the pathways of fatty acid incorporation into adipose tissue.
 ...
PMID:Metabolic alkalosis in diabetic ketosis: a case report. 643 80

We studied the effect of variation at the lipoprotein lipase (LPL) gene locus on the susceptibility of individuals with Type 2 diabetes mellitus to atherosclerotic vascular disease in a population of 126 male and 114 female patients. The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was low in the patients who were homozygous for the presence of the PvuII restriction site (genotype 2-2) (40.9%) compared with those who were heterozygous (genotype 1-2) (57.9%; P = 0.05) or homozygous for the absence of it (genotype 1-1) (61.9%; P < 0.04). In men, a clear gene dosage effect on CHD was seen, the genotype 2-2 patients having the lowest (39.1%), the 1-2 patients an intermediate (49.3%) and the 1-1 patients the highest (61.1%) frequency of coronary disease. Patients with the genotype 2-2 of the HindIII polymorphism (absence of the restriction site) had the highest prevalence of any evidence of CHD (90.0%) compared with the genotype 1-2 (heterozygotes for the presence of the restriction site) (55.4%) or 1-1 (presence of the restriction site) (54.6%; P < 0.03). Stepwise discriminant analysis revealed that in the whole diabetic population the PvuII genotype of the LPL gene was independently and significantly associated with CHD but its effect decreased when the plasma lipids were taken into account. Overall, this study demonstrates the role of the PvuII polymorphism in the LPL gene to modulate the risk for diabetic macroangiopathy in patients with Type 2 diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:DNA polymorphisms at the lipoprotein lipase gene are associated with macroangiopathy in type 2 (non-insulin-dependent) diabetes mellitus. 766 92

Epidemiological studies have elucidated that diabetes mellitus (DM) is one of the risk factors of coronary heart disease and that DM often accompanies dyslipidemia. Dyslipidemia in DM can be classified as either quantitative or qualitative. Although dyslipdemia in DM is affected by the type of DM and glycemic conditions, the characteristics of dyslipidemia in DM, especially in NIDDM are the increase in triglycerides accompanied by the decrease in HDL-cholesterol level. Recently, new commercial kits for measurement of atherogenic lipoproteins which increase in DM are clinically available. The usefulness of these kits in DM was reviewed. Polyacrylamide electrophoresis can detect IDL and Lp(a) qualitatively. It has also become possible to estimate Lp(a) quantitatively by ELISA, TIA and LIA methods. Remnant lipoprotein can be measured in the fraction unbound to anti-apo A1 and anti-apo B100 antibodies by immunoaffinity gel analysis. Apoproteins, apoprotein E phenotype, post-heparin lipoprotein lipase, and Lp AI (HDL with apo AI and without apo AII) can be measured by the commercially available kits. Modified LDLs (glycated, oxidative) increase in DM, but their measurements remain complicated at the moment. Analysis of plasma fatty acids by gaschromatography is useful for dietary assessment. The measurement of these new markers seems to be useful to assess the extent of atherogenic risk in DM.
 ...
PMID:[Plasma fatty acids, lipids, lipoprotein and macroangiopathy]. 778 61

Previous studies with healthy volunteers and non-insulin-dependent diabetic (NIDDM) patients have shown a strong association between overall glucose metabolism and hepatic microsomal enzyme activity. In this study, the effects of 10-day oral administration of phenobarbital (PB), a potent inducer of the hepatic microsomal mixed-function oxidase system, on carbohydrate and lipid metabolism in the basal state and on glucose kinetics during submaximal hyperinsulinemic (5 mU.kg-1.min-1 insulin) clamps were investigated in nondiabetic rats and in rats made diabetic by the intravenous (IV) administration of either low-dose (40 mg/kg) or high-dose (55 mg/kg) streptozocin (STZ). In control rats receiving PB in drinking water (0.5 mg/mL), serum insulin and triglyceride levels were diminished without any change in glucose and cholesterol concentrations in the fed state. Administration of PB in drinking water (0.25 mg/mL) to both groups of diabetic rats decreased their water intake and serum triglyceride levels in the absence of an effect on glucose, insulin, and cholesterol concentrations in the fed state. However, fasting serum glucose levels and basal glucose turnover rates were lower in both groups of diabetic rats receiving PB. PB treatment increased the heparin-releasable lipoprotein lipase (LPL) activity of epididymal fat in both control and low-dose diabetic groups; this was not assessed in the high-dose diabetic group. Neither peripheral glucose utilization nor hepatic glucose production during submaximal insulin clamps was modified by PB treatment in nondiabetic rats. In contrast, PB administration enhanced insulin-mediated peripheral glucose utilization, as well as suppression of hepatic glucose production, in both low-dose and high-dose diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves lipid metabolism in the diabetic rat. 813 83

Twenty patients (18 men, 2 women) with non-insulin dependent diabetes mellitus (NIDDM) were randomized to receive either gemfibrozil 1200 mg daily or placebo for 3 months in a double-blind study. The effect of gemfibrozil on plasma HDL subfraction distribution was studied with sequential and density gradient ultracentrifugation and in gradient gel electrophoresis. The concentrations of apo A-I, apo A-II, Lp A-I and Lp A-I:A-II particles were measured. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and plasma cholesteryl ester transfer protein (CETP) activities were also determined. Gemfibrozil increased the concentration of HDL cholesterol (P < 0.01), which was due to the rise of HDL3 cholesterol (+16%), while in the placebo group these values remained unchanged. Gemfibrozil increased the concentrations of apo A-I(+12.6%, NS), apo A-II (+28.2%, P < 0.01) and Lp A-I:A-II particles (+21.6%, P < 0.06) but there were no changes in the placebo group. Neither gemfibrozil nor placebo had any effect on the concentration of Lp A-I particles. As determined by density-gradient ultracentrifugation, gemfibrozil increased the concentration of cholesterol in the most dense HDL fractions (mean density 1.193 g/ml, +22%, P < 0.05 and mean density 1.158 g/ml, +19.3%, P < 0.05). In gradient gel electrophoresis, the gemfibrozil-induced elevations of the cholesterol and protein were most pronounced in the HDL3a (8.8-8.2 nm) region. Gemfibrozil increased LPL and HL activities by 14.7% (P < 0.05) and by 18.8% (P < 0.01), respectively, while in the placebo group LPL and HL activities remained unchanged. Plasma CETP activity was also increased during gemfibrozil treatment while in the placebo group it remained unchanged. We conclude that gemfibrozil causes multiple changes in plasma HDL metabolism. The gemfibrozil-induced elevation of HDL3 and dense HDL subpopulations may reflect the concerted action of LPL, HL and CETP on plasma HDL metabolism.
 ...
PMID:Effect of gemfibrozil on high density lipoprotein subspecies in non-insulin dependent diabetes mellitus. Relations to lipolytic enzymes and to the cholesteryl ester transfer protein activity. 825 55

A proband with chylomicronemia, pancreatitis, and non-insulin-dependent diabetes (NIDDM) bears two different mutations in exon 3 of the lipoprotein lipase (LPL) gene: a missense mutation, 75Arg-->Ser, inherited through the paternal line and a truncation, 73Tyr-->Ter, through the maternal line. NIDDM appeared to be independently segregating. The R75S mutant was studied in extracts and media from transfected COS-1 cells. Detectable amounts of catalytically competent R75S LPL suggested destabilization of the active homodimer as with exon 5 mutants (Hata et al. 1992. J. Biol. Chem. 267:20132-20139). Hydrolysis of a short-chain fatty acid ester indicated that R75S does not directly affect activation of LPL by apoC-II. Subjects with NIDDM and wild-type LPL, and nondiabetic middle-aged carriers of the 73Tyr-->Ter truncation had moderate hypertriglyceridemia (260-521 mg/dl) and reduced high density lipoprotein cholesterol. A maternal aunt with NIDDM carried the truncation. Her phenotype (triglycerides of 5,300 mg/dl, eruptive xanthomatosis, and recurrent pancreatitis) was as severe as that in homozygotes or compound heterozygotes. We conclude: (a) diabetic carriers of dysfunctional LPL alleles are at risk for severe lipemia; and (b) the physiologic defects in NIDDM may be additive or synergistic with heterozygous LPL deficiency.
 ...
PMID:Mutations in exon 3 of the lipoprotein lipase gene segregating in a family with hypertriglyceridemia, pancreatitis, and non-insulin-dependent diabetes. 832 86

OBJECTIVE--To determine the effects of diabetes on plasma lipoproteins in Pima Indians, to identify metabolic determinants of these differences, and to examine the effects of various modes of diabetes therapy. RESEARCH DESIGN AND METHODS--A series of studies was performed including a population survey of lipoprotein concentrations, kinetic studies of VLDL and LDL metabolism, and studies of the effects of weight loss, sulfonylureas, and high carbohydrate diets. RESULTS--Population data established that diabetes was consistently associated with elevations in total and VLDL TGs and decreases in HDL cholesterol. Metabolic studies indicated multiple alterations in VLDL metabolism induced by NIDDM, including overproduction of VLDL TG, impaired clearance of VLDL TG and apoB, and decreases in adipose tissue lipoprotein lipase. Although changes in LDL concentrations accompanying NIDDM were minimal, the clearance of LDL appeared to be impaired and a higher proportion of VLDL was metabolized without conversion to LDL. There were significant changes in the flux of particles to the LDL compartment. Total and VLDL TG concentrations were found to be inversely related to rates of insulin-mediated glucose disposal, and HDL cholesterol concentrations were positively related to glucose disposal. These relationships between lipoproteins and insulin action were independent of adiposity and insulin, suggesting that insulin resistance may be involved with diabetes-induced changes in VLDL and HDL. Weight loss was associated with decreases in total and VLDL TG, decreases in total and LDL cholesterol, and improvements in the ratio of HDL to LDL cholesterol. Sulfonylurea therapy was associated with lower total and VLDL TGs and lower LDL cholesterol, but little change in HDL. Substitution of complex carbohydrates for saturated fat in the diet showed consistent and significant decreases in total and LDL cholesterol, no decreases in HDL cholesterol, or elevation of total or VLDL TG. CONCLUSIONS--Studies suggest that there are multiple changes in plasma lipoproteins accompanying NIDDM in Pima Indians, but that many of these may be reversed by current modes of hypoglycemic therapy.
 ...
PMID:Diabetes and plasma lipoproteins in Native Americans. Studies of the Pima Indians. 842 93

Six patients with type 2 diabetes underwent detailed metabolic studies before and after a minimum of 3 months' glibenclamide therapy. Treatment was associated with a small but significant increase in body weight. Despite improvements in almost all the measured parameters of glucose homeostasis (plasma glucose, glycosylated haemoglobin (HbA1), hepatic glucose production and insulin-mediated glucose disposal) neither fasting serum triglycerides nor HDL cholesterol changed and apoprotein A1 concentrations actually decreased significantly. NEFA and glycerol in fasting plasma and during the clamp studies did not change significantly with treatment. Post-heparin lipoprotein lipase and hepatic lipase activity did not change significantly. Thus, despite substantial improvements in glycaemic control and insulin sensitivity with sulphonylurea therapy, several aspects of lipid and lipoprotein metabolism remain largely unaffected. This small study suggests either that lipoprotein concentrations in type 2 diabetes are not influenced by insulin sensitivity or that the improvement is offset by another change that occurs during this form of therapy. It also suggests that other forms of therapy will be required to improve these cardiovascular risk factors in type 2 diabetes.
 ...
PMID:The effects of glibenclamide on glucose homeostasis and lipoprotein metabolism in poorly controlled type 2 diabetes. 845 16

Diabetes is frequently associated with the combination of hypertriglyceridemia and low HDL cholesterol level, a known risk factor for cardiovascular disease. We evaluated the frequency of elevated serum triglyceride and the reduced HDL cholesterol levels in Japanese male NIDDM patients. Hypertriglyceridemia (>1.69 mmol/l) and low HDL cholesterol level (<0.91 mmol/l) were frequently found in Japanese male (NIDDM patients (30.4 and 14.2%, respectively). The combined abnormality, i.e., hypertriglyceridemia with concomitant low HDL cholesterol level, was more common in patients with poor glycemic control. We observed that inpatient diet therapy markedly reduced serum triglyceride but serum HDL cholesterol did not change significantly. This is in marked contrast to primary hypertriglyceridemia, in which HDL cholesterol level generally increases in parallel with a reduction in serum triglyceride level. We discuss the defective removal of triglyceride-rich lipoproteins and ineffective HDL production caused by lipoprotein lipase (LPL) deficiency. We also discuss possible correction of this combined abnormality by certain maneuvers that increase LPL activity.
 ...
PMID:Hypertriglyceridemia and low HDL cholesterol in Japanese patients with NIDDM. 867 78

Elevated levels of plasma triglycerides (TG) and reduced concentrations of HDL cholesterol are very common in patients with diabetes, particularly NIDDM. Although regulation of the plasma concentrations of VLDL, the major TG-rich lipoprotein is extremely complex, it is clear from in vivo kinetic studies that increased rates of secretion of VLDL into plasma is almost uniformly present in patients with NIDDM and hypertriglyceridemia. Recent studies at the cellular level indicate that increased fatty acid flux to the liver, also common in NIDDM (and other insulin-resistant states associated with elevated plasma TG levels), will stimulate the assembly and secretion of apoprotein (apo) B-containing lipoproteins by targeting apoB for secretion rather than intracellular degradation. Increased rates of secretion of VLDL into plasma appears to drive the exchange of TG from these lipoproteins for HDL cholesteryl ester. This exchange, which occurs in plasma, is facilitated by cholesteryl ester transfer protein, and generates a TG-enriched HDL that is a substrate for either hepatic lipase or lipoprotein lipase. When the TG in HDL is hydrolyzed, the resultant particle is smaller, and this appears to affect the binding of the major HDL protein, apoA-I. ApoA-I dissociates from the smaller, lipid-poor HDL, and the free apoA-I (molecular weight 28,000) can be filtered by the glomerulus in the kidney and most likely is degraded in renal tubular cells after reabsorption. Thus, increased free fatty acid transport in plasma, a common abnormality in insulin-resistant states, may be the underlying driving force for the two common lipid abnormalities seen in diabetes.
 ...
PMID:Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. 867 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>