Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypolipidaemic effect of a new drug, gemfibrozil (CI-719), was studied for 20 weeks in 20 patients with primary type IIb, III, IV or V hyperlipoproteinaemia. Baseline recordings of serum cholesterol (9.1 mmol/l), triglyceride (3.79 mmol/l) and ultra-centrifugally isolated lipoproteins were obtained during a six-week pretreatment period with stable diet and body weight. With 800 mg of gemfibrozil per day given in two divided doses, the mean serum triglyceride and cholesterol levels were decreased by 44.6% and 10.5% respectively, during 20 treatment weeks. Only 2 patients were completely resistant to the hypolipidaemic action of the drug. Serum triglyceride was brought down to normal levels in 9 subjects. After 12 weeks of treatment the mean VLDL-triglyceride, VLDL-cholesterol, and LDL-triglyceride were reduced by 48.5%, 57.6%, and 22.7% respectively, while the HDL-cholesterol rose by 16%. The LDL-cholesterol increased slightly but significantly during treatment in type IV patients and decreased in type IIb patients. The change of LDL-cholesterol showed an inverse correlation with the initial LDL-cholesterol level (r=-0.87). The postheparin plasma lipoprotein lipase and hepatic lipase activities, determined separately by an immunochemical method, increased during four weeks of gemfibrozil treatment (+18.1% and +20.6% respectively), but neither of these changes was significantly correlated with the changes in any of the serum lipid or lipoprotein levels. Oral glucose tolerance was not influenced by the treatment, but one-hour plasma insulin increased slightly during administration of the drug. One patient discontinued the drug after eight weeks because of generalized allergic eczema, but no other side effects were recorded. It is concluded that gemfibrozil is highly effective in reducing elevated serum VLDL levels. The simultaneous elevation of LDL in type IV patients needs more attention and study. The mechanism of the hypolipidaemic action of the drug is so far obscure, but it might partly be due to an increased efficiency in VLDL removal by an increased activity of lipoprotein lipase.
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PMID:Gemfibrozil: effect on serum lipids, lipoproteins, postheparin plasma lipase activities and glucose tolerance in primary hypertriglyceridaemia. 19 Jun 8

Familial hypertriglyceridemia or hyperlipoproteinemia type I was detected in three siblings aged 6, 11, and 14 of an otherwise normal Turkish family of 10 members. Initial values ranged from 1780 to 3750 mg/100 ml triglycerides in the milky white serum; cholesterol was normal. Lipoprotein pattern on agarose and acrylamide gel revealed a heavy band of chylomicrons and missing HDL; post-heparin lipolytic activity was decreased to about 30% of normal. Chylomicronemia could be induced by a fat-rich (50% of total calories) diet, but not by carbohydrates. On a low fat diet (5%) during hospitalization chylomicrons disappeared, and triglycerides decreased to about 450 mg/100 ml. Phenocopies of hypertriglyceridemia could be excluded. All three patients were the only members of the family who were small, below the third percentile. Their bone age was retarded from 18 to 30 months. There was no indication for an endocrine cause of the growth retardation: four different stimulation tests revealed normal growth hormone response, thyroid and adrenal functions were not impaired; sexual development was normal. Increased glucose assimilation was observed during intravenous and oral glucose load. Peak serum insulin response was above normal during stimulation tests. The possible etiologic role of hypertriglyceridemia in this concomitant growth retardation is discussed.
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PMID:Juvenile familial hypertriglyceridemia and growth retardation. Clinical and biochemical observations in three siblings. 19 55

The effects of a 13-week moderate exercise program on fasting plasma insulin, lipids, and lipoprotein cholesterol concentrations were studied in 32 sedentary, middle-aged men with coronary artery disease. The preponderant component of the exercise program was walking or slow jogging. There was no significant change in the systolic blood pressure and pulse rate product response to a standard exercise load. The high-density lipoprotein-cholesterol (HDL-C) level increased, and the fasting plasma insulin concentration decreased. There were no significant changes in plasma triglycerides or low-density lipoprotein cholesterol levels. In sedentary subjects with coronary artery disease, a modest increase in activity can result in an increase in the HDL-C level and a decrease in the plasma insulin concentration. These changes occurred in the absence of variations in diet, smoking habits, adiposity, or plasma triglyceride concentrations and did not require a cardiovascular training effect.
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PMID:Moderate exercise and high-density lipoprotein-cholesterol. Observations during a cardiac rehabilitation program. 22 33

Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals.
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PMID:Changes in plasma lipoproteins accompanying diet therapy in obese diabetics. 22 83

The effect of gemfibrozil, a new hypolipidaemic compound, on serum lipids, lipoproteins and ophthalmic signs was studied in 20 diabetics during a 28 week trial. Ten of the patients were taking oral hypoglycaemic agents and another ten insulin. Genfibrozil elevated the proportion of alpha-lipoproteins (HDL) (P less than 0.005) in patients on oral agents to the same level as in those using insulin, who experienced no change in HDL. The pre-beta-lipoprotein proportion (VLDL) decreased (P less than 0.001) along with the serum triglyceride level in patients on oral agents only. The proportion of beta-lipoproteins (LDL) remained unchanged in both groups. The serum cholesterol and total lipid levels decreased significantly whether the patients were on oral treatment or insulin. The gemfibrozil was well tolerated. A minor increase in diabetic therapy was made in 9 patients in order to control the blood sugar levels. The ophthalmic signs were generally unchanged.
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PMID:The effect of gemfibrozil on serum lipids in diabetic patients. 39 83

Restudy of 306 "new immigrant Yemenite" Jews, an ethnic group in which, upon their arrival in Israel, no diabetes was detected, revealed, 25 yr after their immigration, an increased incidence of diabetes and higher plasma and lipoprotein-lipid levels. The prevalence of diabetes (defined as "glucose intolerance") rose to 11.8% (13.2% males and 9.7% females). Obesity in females resulted in increased prevalence of diabetes in all age groups, while in males it affected the older age group only. The male/female diabetic ratio was affected by weight status--in the underweight, diabetes was more prevalent in males, in the overweight, the rate of diabetes in females equaled that of males. In nondiabetics (those with normal glucose tolerance), neither the glucose tolerance nor the insulin response deteriorated with aging. Most diabetics had a delayed insulin response. However, about 50% of nondiabetics and diabetics had insulin response peak at 60 min and similar insulin levels. It appears that in newly discovered adult-onset diabetics in this population there is no shortage of insulin, but rather shortage of insulin action. In nondiabetics, the levels of plasma cholesterol and triglycerides (TG) were higher than levels upon their arrival. In diabetics, the plasma TG, cholesterol, and LDL-cholesterol levels were higher when compared to those of nondiabetics, especially in the group of overweight males. Hyperlipoproteinemia was diagnosed in 27.7% of diabetics and 11.0% of nondiabetics. In diabetics, the HDL/LDL cholesterol ratio was found to be reduced, significantly so in overweight diabetics.
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PMID:Diabetes, blood lipids, lipoproteins, and change of environment: restudy of the "new immigrant Yemenites" in Israel. 44 7

Serum lipoproteins, separated by preparative ultracentrifugation and the activity of the plasma enzyme lecithin: cholesterol acyltransferase (LCAT) have been measured in insulin-dependent diabetics, non-insulin-dependent diabetics and in age-matched non-diabetic controls. In the insulin-dependent diabetics, mean total serum cholesterol and high density lipoprotein cholesterol (HDL-C) concentrations were significantly higher than in controls. Non-insulin-dependent diabetics had significantly raised total triglycerides and cholesterol, but HDL-C levels were essentially normal. The increased low density lipoprotein cholesterol (LDL-C) in both diabetic groups was statistically significant in men. A methodological study of HDL separation techniques was carried out to facilitate interpretation of these findings. Mean LCAT activity, by a method reflecting combined enzyme and substrate effects was significantly increased in these diabetic groups. The results confirm recent reports of a raised HDL-C in those insulin-dependent diabetics who are prone to coronary heart disease.
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PMID:Lipoproteins and plasma cholesterol esterification in normal and diabetic subjects. 51 47

The effects of chlorpropamide on serum lipids, lipoproteins and fractional triglyceride removal have been studied over 12 months on 10 maturity onset diabetics not controlled on diet alone. Similar studies were carried out in 6 maturity onset diabetics who had failed to respond to sulphonylureas and 6 new insulin requiring diabetics. In the chlorpropamide treated patients there was an initial fall in serum and VLDL triglyceride but this effect was lost at 12 months. There was no change in fractional triglyceride removal. At 12 months there was a fall in LDL and a rise in HDL choelsterol. An initial improvement in glucose tolerance and insulin secretion was maintained at 12 months. In the insulin treated group the initial fall in serum and VLDL triglyceride was maintained at 12 months and was accompanied by an increase in fractional triglyceride removal. There was also a fall in LDL and a rise in HDL cholesterol at 12 months. The failure of chlorpropamide to maintain the reduction in serum and VLDL triglyceride could be of importance in the genesis of coronary heart disease in maturity onset diabetics. The fall in LDL and rise in HDL cholesterol found both with chlorpropamide and insulin might be beneficial.
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PMID:The effects of chlorpropamide and insulin on serum lipids, lipoproteins and fractional triglyceride removal. 70 Feb 75

The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls.
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PMID:A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with type 1 (insulin-dependent) diabetes mellitus. 128 18

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10


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