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OBJECTIVE: To compare the lipid-lowering efficacies of simvastatin and gemfibrozil in NIDDM patients with combined (mixed) hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). RESEARCH DESIGN AND METHODS: Patients with primary dyslipidemia and NIDDM were recruited for this double-blind, double-dummy comparison study from 10 Finnish centers. After a 4-week placebo run-in period, they were randomly assigned to simvastatin or gemfibrozil. The simvastatin group (n = 47) received 10 mg once nightly for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The gemfibrozil group (n = 49) received 600 mg twice daily throughout the 24 weeks. The lipid-lowering efficacies of both drugs were compared in all patients as well as separately in patients with CHL and IHC. RESULTS: In all patients, simvastatin reduced LDL and total cholesterol and the LDL-to-HDL cholesterol ratio more effectively, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The drug effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30-40% in both phenotypes. Gemfibrozil caused a 15% reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15-30% reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL (50% and more) and in IHC (40%) patients, with 12-18% increases in HDL cholesterol in these groups. CONCLUSIONS: Simvastatin is useful in both CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels.

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OBJECTIVES: To examine the acute effects of captopril administration on insulin sensitivity in normotensive type 1 diabetic patients. DESIGN: An euglycaemic insulin clamp (150 min) was performed in a randomized order twice in each subject: once with the oral administration of captopril (25 mg), once with placebo, both given in the beginning of the insulin infusion. SETTING: The study was performed at the clinical research laboratory of Helsinki University Hospital, Second and Third Departments of Medicine. SUBJECTS: We studied seven male, normotensive type 1 diabetic patients with normal body weight, duration of diabetes 15 +/- 2 years, HbA1 9.8 +/- 0.7% and daily insulin dose 47 +/- 4 units. In addition, nine matched healthy control subjects were examined. RESULTS: During placebo administration glucose disposal rate in the diabetic patients was not significantly different from that in the control subjects. Captopril administration reduced blood pressure in both groups, whereas glucose disposal rate did not change significantly in diabetic or control subjects. When diabetic and control subjects were analysed together, captopril decreased glucose disposal by 9% (P < 0.05). CONCLUSIONS: Acute captopril administration does not improve insulin sensitivity in normotensive type 1 diabetic patients or control subjects.

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We studied the 1-year response and predictors of the response to combination therapy with evening insulin and oral agents in NIDDM patients with a secondary failure. Injection of intermediate-acting (Monotard HM) or long-acting (Ultratard HM) insulin was added to previous oral therapy in 17 diabetics (of mean age (+/- SD) 54 +/- 2 years, BMI 27.6 +/- 0.5 kg m-2). The initial insulin dose was in the range 10-16 U, and the mean dose was 23 +/- 2 U d-1 at 12 months. During the year, combination therapy reduced the mean fasting blood glucose concentration (12.7 +/- 0.6 vs. 8.4 +/- 0.7 mmol l-1, P less than 0.001) and HbA1 (10.7 +/- 0.3 vs. 9.8 +/- 0.4%, P less than 0.01). Body weight increased by 4.4 +/- 0.7 kg (P less than 0.001). The serum cholesterol concentration decreased by 14% (P less than 0.01), but serum triglyceride and HDL-cholesterol levels remained unchanged. Elevation of serum triglycerides and plasma free fatty acids (FFAs) at baseline predicted a poor long-term outcome to this mode of therapy. In conclusion, the addition of evening injections of insulin to oral therapy improves glycaemic control in poorly controlled NIDDM patients. However, initial hypertriglyceridaemia predicts a poor long-term outcome to evening insulin supplementation.

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Despite the well-documented efficacy of lovastatin, a wide inter-individual variation in treatment responses has been observed. The aim of the present study was to investigate the possible roles of apolipoprotein E (apo E) phenotype and apolipoprotein B (apo B) XbaI genotype on this variation. The apo E phenotype was determined in 232 subjects (78 cases of familial hypercholesterolaemia [FH] and 154 cases of non-familial hypercholesterolaemia [non-FH]) and the apo B XbaI genotype was determined in 211 subjects (67 cases of FH, 144 cases of non-FH). Depending on their baseline total serum cholesterol levels, these patients used a starting dose of lovastatin of either 20 or 40 mg nightly. After 6 weeks of therapy, slightly but significantly smaller reductions in LDL-cholesterol were observed in patients with the E4/3 phenotype compared with those with the E3/3 phenotype in non-FH with lovastatin 20 mg (-20 vs. -28%; P = 0.043) and in total cholesterol in FH with lovastatin 40 mg (-23 vs. -27%; P = 0.023). No significant differences were found in non-FH patients starting with lovastatin, 40 mg. After doubling of the lovastatin doses, all treatment responses became similar among apo E phenotypes. Moreover, when all patients using lovastatin 40 mg either at 6 or 12 weeks were pooled (n = 224), no differences in treatment responses were observed between the E3/2, E3/3, E4/3 and E4/4 phenotypes. The apo B XbaI genotype did not affect the hypocholesterolaemic efficacy of lovastatin in any of the patient groups. Thus our results indicate that inter-individual variation in the treatment response to lovastatin in both familial and non-familial hypercholesterolaemia is mainly due to factors other than the apo E phenotype or apo B XbaI genotype.

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To determine whether intensive insulin therapy has the same beneficial effects on lipoprotein composition that it has been shown to have in insulin-dependent diabetes mellitus (IDDM) on the routinely measured plasma lipids, we studied 10 patients after 6 months of conventional therapy (CIT) and again after 6 months of therapy with continuous subcutaneous insulin infusion (CSII). While the mean of home blood glucose levels (8.1 +/- 0.5 v 7.9 +/- 0.5 mmol/L) decreased no further, plasma triglycerides (TG) (CIT, 102.7 +/- 25.0; CSII, 89.6 +/- 27.1 mg/dL; P less than .001) decreased after CSII, and high-density lipoprotein cholesterol (HDL-C) increased significantly, primarily as a consequence of an increase in HDL2 (CIT, 12.2 +/- 6.0; CSII, 18.1 +/- 6.3 mg/dL; P less than .02). Low-density lipoprotein cholesterol (LDL-C) was unchanged (CIT, 82.2 +/- 32; CSII, 84.0 +/- 27.8 mg/dL). After CIT, two indices of lipoprotein surface composition were altered: (1) the free cholesterol (FC) to lecithin ratio, which is a new cardiovascular risk factor, was abnormally increased in plasma, very-low-density lipoprotein (VLDL) + LDL, and HDL, and (2) the sphingomyelin to lecithin ratio, an index of the surface rigidity of lipoproteins, was increased in the HDL subfractions. While CSII treatment resulted in favorable changes in whole plasma lipids, it failed to correct these disturbances in composition. Since the participation of lipoproteins in certain steps in reverse cholesterol transport appears to be impaired when their surface constituents are altered, persistence of these disturbances may sustain the increased cardiovascular risk of IDDM patients, even when their clinical control is very good and their plasma lipids are normal.

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Subanalyses of previous multicenter studies comparing lovastatin and gemfibrozil were carried out to evaluate the merits of these agents in patients with different serum lipid phenotypes (type 2a and 2b hyperlipoproteinemia). Regardless of phenotype, lovastatin was more effective in lowering LDL-cholesterol, while gemfibrozil had a greater triglyceride-lowering and HDL-cholesterol-increasing effect. Patients with type 2a phenotype benefited (in terms of serum lipid pattern) more from lovastatin. In type 2b hyperlipoproteinemia, more patients taking lovastatin than gemfibrozil reached both treatment goals defined by the European Atherosclerosis Society, (LDL-cholesterol 4.0 mmol/l and triglycerides 2.3 mmol/l). In many patients these goals could not be met suggesting that multiple drug therapy may be indicated in part of the patients with type 2b hyperlipoproteinemia.

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We used a modification of the polymerase chain reaction (PCR), involving two pairs of oligonucleotide primers, to detect a mutation in the low-density lipoprotein (LDL) receptor gene, commonly occurring among patients with familial hypercholesterolemia (FH) in Finland. This mutation, called FH-Helsinki, involves a large (about 9500 base pairs, bp) deletion in the LDL receptor gene extending from intron 15 to exon 18. For the PCR, one pair of primers was designed to cover both sides of the deletion in its immediate vicinity. In the presence of the deletion, the primers were brought close enough to each other to allow the amplification and electrophoretic detection of a 300-bp amplification product. In the absence of the deletion, no amplification occurred and this band accordingly was not visible in the gel. To render the interpretation of the results unequivocal, we designed a second pair of oligonucleotide primers. This pair of primers allowed another amplification product (158 bp) to appear in samples containing a normal exon 17, i.e., in DNA specimens from healthy subjects and FH heterozygotes with or without the FH-Helsinki deletion. The technique is easy to perform, avoids the use of radioactive reagents, and is applicable to the detection of any extensive DNA deletion.

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The 3-year efficacy of lovastatin alone or in combination with colestipol was evaluated in 54 patients with type 2 hyperlipoproteinemia (22 non-familial and 32 familial hypercholesterolemic patients). A sufficient and sustained reduction in LDL cholesterol was achieved in non-familial hypercholesterolemia with lovastatin alone (average dose 74 mg/day, range 40-80 mg/d), whereas combination therapy with lovastatin 80 mg/d and colestipol (average dose 11.9 g/d, range 5-20 g/d) was required in familial hypercholesterolemia. The percentage changes from baseline at 3 years in serum LDL cholesterol, HDL cholesterol and total triglycerides were in the lovastatin-only group -53%, +10% and -15%, respectively, and in the two-drug group -58%, +22% and -18%, respectively. A subgroup analysis in patients with non-familial hypercholesterolemia indicated that the lipid-modifying effects of lovastatin were similar in type 2A and 2B phenotypes, except for a greater triglyceride lowering effect in type 2B. The lovastatin-alone regimen was well tolerated, whereas addition of colestipol caused subjective side effects in many patients. Serious side effects or discontinuations due to therapies did not occur. Both therapies caused slight but significant increases (within normal limits) in average serum transaminase levels. After 36 months a significant rise of 1.7 kg in mean body weight was observed in the lovastatin-only group. The ophthalmological follow-up did not reveal any cataractogenic effect attributable to treatment during the 3.8-year follow-up period.

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A subanalysis was performed on data acquired from 67 subjects having serum cholesterol levels of 6.2 mmol/l or above (greater than or equal to 240 mg/dl) and triglyceride levels of 2.25 to 4.00 mmol/l (199-354 mg/dl) (excluding patients with familial hypercholesterolemia), who were participating in a multicenter study comparing lovastatin and gemfibrozil, to evaluate the role of these agents in the treatment of combined hyperlipidemia (type IIb phenotype). In stratum 1 (cholesterol measures of 62.-7.79 mmol/l [240-301 mg/dl]), patients received either lovastatin 20 mg nightly (n = 17) or gemfibrozil 600 mg twice daily (n = 8), and in stratum 2 (cholesterol levels greater than or equal to 7.8 mmol/l [greater than or equal to 302 mg/dl]), patients received either lovastatin 40 mg nightly (n = 23) or gemfibrozil 600 mg b.i.d. (n = 19) for 6 weeks. Low-density lipoprotein (LDL) cholesterol levels were reduced significantly more by lovastatin than by gemfibrozil (stratum 1, -23 versus +1%, stratum 2, -34 versus -12%, respectively). A treatment goal of 4.0 mmol/l (155 mg/dl) for LDL cholesterol was achieved by 59 and 35% of patients receiving lovastatin and by 0 and 11% of patients receiving gemfibrozil in strata 1 and 2, respectively. Gemfibrozil was more effective in reducing triglyceride levels and in increasing high-density lipoprotein (HDL) cholesterol in both strata, although increases in HDL/LDL cholesterol ratios were greater with lovastatin. We conclude that, although lovastatin was more useful in normalizing LDL cholesterol, neither agent was ideal for all patients with combined hyperlipidemia. Further development of treatment regimens is called for in this group of patients.

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We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulin-dependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha and TX synthesis by measuring TXB2 in serum and urine. In the resting state, prostanoid excretion and concentrations were similar in diabetic and control subjects. During 40 min of ergometric cycling exercise, the urinary excretion of 6-keto-PGF1 alpha (a hydration product of vasodilatory PGI2) increased 5.8-fold more in the 12 control subjects than in the 15 diabetic patients (P less than .02). Serum TXB2 concentration rose similarly in diabetic patients and control subjects (P less than .05). During a 75-km competitive cross-country ski race (7 h, 30 min), urinary excretion of 6-keto-PGF1 alpha rose 1.9-fold in 7 diabetic (P less than .05) and 3.3-fold in 10 control (P less than .001) subjects, whereas urinary dinor excretion, reflecting vascular PGI2 synthesis more closely, increased only in the control subjects (P less than .01). Urinary TXB2 excretion remained unchanged in both groups during long-term exercise. These data suggest that diabetic patients have normal PGI2 and TXA2 synthesis in the resting state but diminished PGI2 response to both acute and prolonged exercise.

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A specific type of gene mutation affecting the LDL receptor has been found in many Finnish patients with familial hypercholesterolemia (FH). The mutant allele is characterized by a 9.5-kb deletion extending from intron 15 to exon 18. Molecular cloning and sequencing of a cDNA segment corresponding to the deleted allele indicated that the mutant receptor differs radically from the normal one because of loss of the domains encoded by exons 16, 17, and 18. The carboxy-terminal portion of the normal receptor, comprising the amino acids 750-839, has been replaced by an unrelated stretch of 55 amino acids. The mutant allele was found to occur in 23 (50%) of 46 unrelated FH patients with an established functional defect in the LDL receptor. In cultured fibroblasts from the FH patients with the 9.5-kb deletion, both receptor-mediated binding and internalization of 125I-LDL were lower than normal, the former, on average, by 25%, and the latter, on average, by 50%. This combined functional defect probably results from both impaired attachment and impaired internalization of the mutated receptor. It remains to be investigated whether this Finnish type of LDL receptor gene mutation, here designated FH-Helsinki, occurs in other ethnic groups.

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An XbaI restriction fragment length polymorphism (RFLP) within the coding region of the apolipoprotein B (apoB) gene has been found to be associated with serum cholesterol and triglyceride levels in several populations. Mutations in another genetic locus, the low density lipoprotein (LDL) receptor gene, give rise to familial hypercholesterolemia (FH), a disease characterized by hypercholesterolemia, tendon xanthomas and atherosclerosis. We determined the XbaI genotypes and serum lipoprotein levels of 120 unrelated patients with the heterozygous form of FH. A non-parametric analysis of variance showed a significant association between elevated serum total cholesterol concentration (P less than 0.05), serum LDL-cholesterol concentration (P less than 0.025) and the presence of the XbaI restriction site (X2 allele). Thus, patients homozygous for the presence of the XbaI restriction site (genotype X2X2, n = 28) had on average a 14% higher serum total cholesterol level and a 21% higher serum LDL-cholesterol level than those homozygous for the absence of this site (genotype X1X1, n = 29); patients heterozygous for the XbaI restriction site (genotype X1X2, n = 63) had intermediate serum total and LDL-cholesterol levels. No significant differences were seen in serum triglyceride or high-density lipoprotein (HDL)-cholesterol values between these patient groups. These data demonstrate that genetic polymorphism of the principal ligand for the LDL receptor, apoB, may contribute to serum cholesterol regulation, even in patients with grossly distorted cholesterol homeostasis.

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Increased gluconeogenesis contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). We examined whether insulin inhibits gluconeogenesis from lactate by altering the fate of lactate and/or by reducing lactate flux. Seven patients with NIDDM (age 51 +/- 4 yr, body mass index 28 +/- 2 kg/m2) were studied before and 3 wk after achieving normoglycemia with evening insulin therapy. Basal glucose production (Ra) and utilization were measured overnight [( 3-3H]glucose infusion from 9 P.M. to 8 A.M.) and lactate turnover and conversion to glucose between 4 and 8 A.M. [( U-14C]lactate infusion) before and after insulin therapy. During insulin therapy, fasting plasma glucose decreased from 188 +/- 13 to 99 +/- 7 mg/dl (P less than 0.001) due to inhibition of glucose Ra from 3.0 +/- 0.1 to 2.2 +/- 0.1 mumol.kg-1.min-1 (P less than 0.005). Plasma free insulin increased from 6 +/- 1 to 11 +/- 1 microU/ml (P less than 0.005). Plasma lactate concentrations (1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmol/l before vs. after insulin therapy) and the lactate turnover rate (15.6 +/- 0.9 vs. 14.2 +/- 0.8 mumol.kg.min) remained unchanged, whereas the amount of glucose formed from lactate decreased from 2.0 +/- 0.1 to 1.4 +/- 0.2 mumol.kg-1.min-1 (P less than 0.02) and the percent of lactate turnover converted to glucose decreased from 26 +/- 1 to 20 +/- 2% (P less than 0.05). We conclude that insulin inhibits overnight glucose Ra from lactate by decreasing the proportion of lactate diverted towards gluconeogenesis rather than by altering lactate availability or total flux.

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We studied the clinical effectiveness and mechanism underlying the glucose-lowering effect of evening insulin therapy. Nocturnal profiles of blood glucose, plasma free fatty acid (FFA), glycerol, and lactate and overnight glucose kinetics [( 3-3H] glucose infusion) were measured in 15 non-insulin-dependent diabetic (NIDDM) patients with a relative body weight of 128 +/-4% who were poorly controlled with oral therapy alone. The patients were studied before and 2 wk and 3 mo after bedtime insulin (23 +/- 3 IU) was given in addition to oral therapy. An early-morning rise in blood glucose (greater than 31 mg/dl = 1.5 mM) was present in two-thirds of the patients and was associated with an overnight rise in plasma FFA and an increase in glucose production (Ra) during the early-morning hours (change 0.42 +/- 0.10 mg.kg-1.min-1, P less than .05, between 0300 and 0800). The overnight mean levels of blood glucose, plasma FFA, and serum insulin averaged 212 +/- 9 vs. 137 +/- 11 vs. 133 +/- 11 mg/dl (P less than .001), 674 +/- 61 vs. 491 +/- 57 vs. 484 +/- 36 microM (P less than 0.01) and 12.7 +/- 1.6 vs. 18.1 +/- 2.2 vs. 20.7 +/- 2.4 microU/L (P less than .01) before and 2 wk and 3 mo after the combination therapy. The decrements in overnight glucose and FFA levels after 2 wk of bedtime insulin therapy were closely correlated (r = .86, (P less than .001). The nocturnal profile of plasma lactate was similar before and during bedtime insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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A randomized, double-blind 12-week comparison of lovastatin and gemfibrozil in the treatment of patients with primary hypercholesterolemia with normal or moderately elevated triglycerides was performed in 334 patients from 19 centers in Finland. Patients with "high" total serum cholesterol (240 to 300 mg/dl) constituted Stratum 1 and patients with "very high" total serum cholesterol (greater than 300 mg/dl) constituted Stratum 2. In Stratum 1, patients were randomly assigned to either lovastatin 20 mg nightly or gemfibrozil 600 mg twice daily, and in Stratum 2 to either lovastatin 40 mg nightly or gemfibrozil 600 mg twice daily. In both strata, the lovastatin dose was doubled after 6 weeks if serum cholesterol remained greater than 200 mg/dl. Ninety-two and 93% of the patients doubled their dose in Strata 1 and 2, respectively, resulting in average doses of 38.5 mg/day (Stratum 1) and 77.4 mg/day (Stratum 1) and 77.4 mg/day (Stratum 2) by week 12. The dose of gemifibrozil was kept constant. Lovastatin reduced low-density lipoprotein (LDL) cholesterol by 31 and 42% in Stratum 1 and 2, respectively. The corresponding reductions achieved by gemfibrozil were 13 and 18%. In both strata, as well as in patients with Type IIa and IIb hyperlipoproteinemia, lovastatin was approximately 2 to 4 times as effective as gemfibrozil in lowering LDL cholesterol. Although both drugs increased high-density lipoprotein (HDL) cholesterol concentrations, gemfibrozil was 1.5 to 3 times more effective. LDL/HDL cholesterol ratios decreased significantly more during lovastatin therapy. Both drugs reduced serum triglyceride levels, but gemfibrozil was much more effective.(ABSTRACT TRUNCATED AT 250 WORDS)

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In order to compare the effects of lovastatin and probucol on lipoprotein profiles, we treated 32 familial hypercholesterolemia (FH) heterozygotes and 26 patients with non-familial hypercholesterolemia for 14 weeks with either probucol (1 g/d) or lovastatin (40-80 mg/d) in a randomized double-blind study. Lovastatin at 80 mg/d reduced low density lipoprotein (LDL)-cholesterol and apo B by more than 40% in both familial and non-familial hypercholesterolemia (non-FH). Probucol reduced LDL-cholesterol by 10-17% while LDL-apo B levels were not influenced at all (FH) or fell by 13% (non-FH). Analysis of LDL composition demonstrated that the LDL-cholesterol lowering effect of probucol in FH was entirely due to reduction in the proportion of cholesterol in LDL with no reduction in LDL mass. Serum high density lipoprotein2 (HDL2)-cholesterol levels fell by 27-33% during probucol, whereas HDL2-cholesterol increased by 10-18% with lovastatin 80 mg/d. These changes in HDL2 were not mediated by lipoprotein lipase or hepatic lipase, both of which are known to participate in regulation of this lipoprotein.

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The effect of guar gum on glucose and lipid metabolism and on body insulin sensitivity was examined in nine type 1 diabetic patients treated with continuous subcutaneous insulin infusion. The study was done in a randomized, double-blind, crossover fashion with either guar gum or a placebo added to the usual diet four times per day for 4 wk each. Blood glucose levels after breakfast and lunch and daily insulin requirements were significantly lower during the guar-gum than the placebo diet. After a 4-wk guar-gum supplementation, blood glucose response to a test meal was significantly reduced by guar gum compared with the placebo. Hemoglobin A1 (HbA1) and insulin sensitivity remained unchanged. Serum total cholesterol fell by 21% (p less than 0.025). Thus, guar gum can reduce postprandial blood glucose, insulin requirements, and serum total cholesterol levels in type 1 diabetic patients.

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To study the effects of rigorous insulin therapy on serum lipoproteins in patients with noninsulin-dependent diabetes not controlled with oral agents only, we measured serum lipoproteins, apoproteins, lipolytic enzymes, and glucose disposal using an insulin clamp technique before and after 4 weeks of insulin therapy. Lipoproteins were isolated by ultracentrifugation and high density lipoprotein (HDL) subfractions, by rate-zonal density gradient ultracentrifugation. The group included 11 women and eight men (age 58 +/- 1 years and RBW 125 +/- 4%). Body weight, glycosylated hemoglobin, mean diurnal glucose, plasma free insulin, and glucose uptake (M-value) were 75 vs. 76 kg; 11.9 vs. 8.9%; 234 vs. 124 mg/dl; 12 vs. 27 microU/ml; and 5.0 +/- 0.4 vs. 7.1 +/- 0.6 mg/kg/min before and after insulin therapy, respectively. After insulin therapy there was a decrease of very low density lipoprotein (VLDL) triglyceride (-60%, p less than 0.001) but an increase of HDL2 cholesterol (+21%, p less than 0.001); HDL2 phospholipids (+38%, p less than 0.001); HDL2 proteins (+23%, p less than 0.01); and HDL2 mass (127 +/- 11 vs. 158 +/- 12 mg/dl, p less than 0.001). There was a decrease of HDL3 cholesterol (-13%, p less than 0.05); HDL3 phospholipids (-16%, p less than 0.05); HDL3 proteins (-18%, p less than 0.001); and HDL3 mass (179 +/- 6 vs. 146 +/- 6, p less than 0.01). Zonal profiles showed a redistribution of particles from HDL3 to HDL2. Serum apo A-I increased (p less than 0.05), apo A-II remained constant, but apo B decreased (-29%, p less than 0.001). The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p less than 0.001). The changes of VLDL and HDL subfractions were not explained by respective changes of the blood glucose, free insulin, or M-value. The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.

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We examined in 2 consecutive years the effect of a 75-km (greater than 7 h) cross country skiing on dietary and insulin requirements and glycaemic control in 9 Type 1 (insulin-dependent) diabetic patients. In the first year, the patients were hyperglycaemic (20.9 +/- 1.8 mmol/l) before the race due to excessive carbohydrate loading (65 g) and reduction (by 58%) of short-acting insulin for breakfast. In the second year, breakfast included less carbohydrate (40 g) and more protein, and the morning short-acting insulin was reduced by 35%. With this adjustment of therapy the pre-exercise hyperglycaemia was less (p less than 0.05). The morning intermediate-acting insulin was reduced by 28 and 38% in consecutive years. During both races carbohydrate intake approximated 40 g/h, and blood glucose was maintained at near normal levels after 33 km of skiing. Hypoglycaemia did not occur during exercise, but one patient had symptomatic hypoglycaemia after finishing the second race. The day after exercise insulin sensitivity was increased in all four patients studied. Insulin treated patients can perform strenuous long-term exercise and maintain near normoglycaemia with a proper adjustment of therapy. Augmented insulin sensitivity may contribute to post-exercise hypoglycaemia.

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