Causes of death and associated factors among patients with non-insulin-dependent diabetes mellitus in Taipei, Taiwan.

A cohort of 766 patients with non-insulin-dependent diabetes mellitus (NIDDM) from a general teaching hospital in Taipei, Taiwan were followed prospectively to assess survival experience and associated risk factors. Data were abstracted from the medical records and additional information was obtained from patients or their closest relatives using a structured questionnaire. Date and cause of death were determined from death certificates. Standardized mortality ratios were calculated by the direct method. Chi2-Square test and Cox's proportional hazard analysis were used to control for potential confounders. During a median follow-up of 3.5 years (range 1 month to 4.6 years), 131 deaths occurred. Of these, 29.8% were due to cardiopulmonary disease (ICD 401-429), 13.0% due to cerebrovascular disease (ICD 430-438), 13.0% due to acute diabetes metabolic complications (250.1, 250.2), and 11.4% due to nephropathy (580-589). Adjusted for age, people with NIDDM had 2.2 (95% CI 1.6-2.9) times the risk of death than members of the general population, and cause-specific standardized mortality ratios were: CPD 4.6, nephropathy 8.8, cerebrovascular disease 1.9, and neoplasm 0.7. Age, fasting plasma glucose, hypertension, and proteinuria were positively and independently associated with all-cause mortality (P < 0.05 for each). Thus, NIDDM patients have higher mortality rates than the general population in Taiwan, and age, fasting plasma glucose, hypertension, and proteinuria are associated with this excess risk. Proper application of available interventions may control these factors with a consequent reduction in mortality. Particular attention is needed to prevent deaths from the acute metabolic complications of diabetes.

Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol.

Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios.

Insulin resistance in patients with Klinefelter's syndrome and idiopathic gonadotropin deficiency.

Patients with Klinefelter's syndrome (KS) have hypergonadotropic hypogonadism and have a higher incidence of diabetes mellitus. Patients with idiopathic gonadotropin deficiency (IGD) also have hypogonadism but have no proven impaired glucose metabolism. Because high serum testosterone concentrations are thought to correlate with insulin resistance, we assessed the relationship of testosterone concentration with insulin resistance in patients with KS or IGD and normal subjects. Seven patients with KS, six with IGD, and seven normal individuals (controls) were enrolled. Insulin resistance was evaluated by two methods: the total area under the curve (AUC) and the incremental AUC of serum insulin concentrations in response to a 75-g oral glucose load, and the insulin suppression test. KS patients had significantly higher follicle-stimulating hormone and luteinizing hormone concentrations than the normal controls, while IGD patients did not. The plasma testosterone concentrations were significantly lower in both KS and IGD groups than in controls. The incremental AUC and total AUC were higher in both KS and IGD patients than in normal subjects. The steady-state plasma glucose concentrations of the KS and IGD groups were significantly higher than that of the normal group, while the steady-state plasma insulin concentrations were similar in all three groups. After log transformation, the plasma testosterone concentration was negatively related to steady-state plasma glucose concentration in all three groups (r = -0.58, p = 0.019). In conclusion, insulin resistance was consistently noted in patients with KS and IGD. Plasma testosterone concentration is inversely related to insulin resistance.

An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.

OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast. RESULTS: Using the intention-to-treat analysis, there were greater reductions in (mean [95% CI]) HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1-h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [-2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group. CONCLUSIONS: In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.

Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations.

Gemfibrozil or placebo was administered for 3 months to 24 individuals with endogenous hypertriglyceridemia and normal glucose tolerance. Mean ( +/- SEM) fasting plasma triglyceride (TG) concentrations decreased (4.01 +/- 0.55 to 1.34 +/- 0.12 mmol/L; P < 0.001) and high density lipoprotein cholesterol concentrations increased (0.54 +/- 0.03 to 0.67 +/- 0.04 mmol/L; P < 0.001) in gemfibrozil-treated patients, associated with lower (P < 0.01-0.001) plasma free fatty acid and TG concentrations when measured at hourly intervals in response to breakfast (0800 h) and lunch (1200 h). However, day-long plasma glucose and insulin responses to meals in the 2 groups were similar before and after treatment, as were the steady state plasma glucose and insulin concentrations at the end of a 180-min infusion of somatostatin, insulin, and glucose. Thus, marked decreases in both plasma TG and free fatty acid concentrations seen in association with gemfibrozil neither enhanced insulin-mediated glucose disposal nor lowered ambient plasma insulin concentrations in patients with endogenous hypertriglyceridemia.

Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22.

Resistance to insulin-mediated glucose disposal is a common finding in patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as in nondiabetic individuals with hypertension. In an effort to identify the generic loci responsible for variations in blood pressure in individuals at increased risk of insulin resistance, we studied the distribution of blood pressure in 48 Taiwanese families with NIDDM and conducted quantitative sib-pair linkage analysis with candidate loci for insulin resistance, lipid metabolism, and blood pressure control. We found no evidence for linkage of the angiotensin converting enzyme locus on chromosome 17, nor the angiotensinogen and renin loci on chromosome 1, with either systolic or diastolic blood pressures. In contrast, we obtained significant evidence for linkage or systolic blood pressure, but not diastolic blood pressure, to a genetic region at or near the lipoprotein lipase (LPL) locus on the short arm of chromosome 8 (P = 0.002, n = 125 sib-pairs, for the haplotype generated from two simple sequence repeat markers within the LPL gene). Further strengthening this linkage observation, two flanking marker loci for LPL locus, D8S261 (9 cM telomeric to LPL locus) and D8S282 (3 cM centromeric to LPL locus), also showed evidence for linkage with systolic blood pressure (P = 0.02 and 0.0002 for D8S261 and D8S282, respectively). Two additional centromeric markers (D8S133, 5 cM from LPL locus, and NEFL, 11 cM from LPL locus) yielded significant P values of 0.01 and 0.001, respectively. Allelic variation around the LPL gene locus accounted for as much as 52-73% of the total interindividual variation in systolic blood pressure levels in this data set. Thus, we have identified a genetic locus at or near the LPL gene locus which contributes to the variation of systolic blood pressure levels in nondiabetic family members at high risk for insulin resistance and NIDDM.

Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy.

Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected in various pathophysiologic states. However, little is known about T3S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3 concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T4 and free T4 concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T3S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T3S and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p < 0.001). In summary, significant increases in serum and urine T3S levels were noted in T4-treated patients with subnormal serum TSH and borderline elevated T4. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T3S may serve as an index for the evaluation of T4-treated patients with elevated levels of T4.

Effect of glipizide treatment on response to an infused glucose load in patients with NIDDM.

OBJECTIVE: This study was initiated to compare the effect of sulfonylurea treatment on the response to an infused glucose load of patients with non-insulin-dependent diabetes mellitus (NIDDM) at a basal insulin concentration and in response to physiological hyperinsulinemia. RESEARCH DESIGN AND METHODS: We used the insulin suppression test, in which subjects were infused for 180 min with somatostatin, exogenous insulin, and glucose. Since similar steady-state plasma insulin (SSPI) concentrations are reached in all subjects, the resultant steady-state plasma glucose (SSPG) concentration permits comparison of the ability of a given individual to maintain glucose homeostasis in response to the infused glucose load. RESULTS: We studied 15 nonobese patients at two different SSPI concentrations, before and after glipizide treatment, at basal (68 +/- 4 pmol/l) and high (470 +/- 31 pmol/l) levels. Values for SSPG concentrations were lower after treatment at both the basal (15.3 +/- 0.5 vs. 18.5 +/- 0.6 mmol/l; P < 0.001) and the high (10.6 +/- 0.7 vs. 14.2 +/- 0.7 mmol/l; P < 0.001) SSPI concentrations. To compare the responses of each patient before and after treatment, we calculated the fractional glucose metabolic rate, i.e., (glucose infusion rate--urinary glucose loss) divided by SSPG. To provide an alternative method of comparing the effect of sulfonylurea treatment, we divided the incremental increase in fractional metabolic glucose rate between the studies done at the low and high SSPI by the incremental increase in SSPI between the two studies (insulin sensitivity index [SI]). CONCLUSIONS: The results of these calculations indicated that glipizide treatment was associated with a significant increase in fractional glucose metabolic rate at a basal insulin concentration (29 +/- 3 to 42 +/- 2 ml.m-2.min-1, P < 0.001), and in response to the incremental change in SSPI (14 +/- 4 to 23 +/- 3 ml.m-2.min-1, P < 0.02). Finally, SI also increased in association with sulfonylurea (0.24 +/- 0.06 to 0.43 +/- 0.07 ml.m-2.min-1/microU.ml-1, P < 0.001).

Suppression of non-esterified fatty acid concentrations by insulin in patients with hypertension.

BACKGROUND: Recent studies have suggested that insulin resistance may be involved in the development of hypertension. Although skeletal muscle accounts for the majority of peripheral insulin resistance, the effect of insulin on adipose tissue, (i.e., antilipolysis) has rarely been defined in hypertensive patients. To understand the effect of high blood pressure on adipose tissue lipolytic activity in vivo, plasma non-esterified fatty acid (NEFA) concentrations at basal insulin, and during physiological hyperinsulinemic state was compared in patients with essential hypertension and a group of normotensive subjects. METHODS: Twenty patients with untreated essential hypertension and 20 age, sex, body mass index (BMI)-matched normotensive subjects were studied. Oral glucose tolerance test (OGTT) in response to a 75-g oral glucose load was carried out for three hours after an overnight fasting. On separate morning, modified insulin suppression test was performed for three hours, which involved a constant infusion of insulin (25 mU/m2/min) glucose (240 mg/m2/min) and somatostatin (350 micrograms/h). The four values obtained every 10 min at last half hour were read as steady state plasma glucose (SSPG), insulin (SSPI) and final NEFA concentrations. RESULTS: Patients with hypertension had significantly higher fasting plasma insulin (101 +/- 9 vs 69 +/- 8 pmol/L, p < 0.02) and NEFA (543 +/- 38 vs 453 +/- 25 mumol/L, p < 0.05) concentrations compared to normotensive subjects. In response to OGTT, the plasma glucose and insulin concentrations increased significantly in the hypertensive group when compared with normotensive group (p < 0.05 and p < 0.01, respectively), whereas plasma NEFA concentrations were suppressed to a similar extent in these two groups. During modified insulin suppression test, the mean SSPG concentrations were significantly higher (10.1 +/- 0.7 vs 7.8 +/- 0.8 mmol/L, p < 0.01) in patients with hypertension compared with normal subjects despite that the mean SSPI concentrations were similar. Plasma NEFA concentrations fell markedly during the period of physiological hyperinsulinemia and achieved similar levels during the last 30 min of infusion in both hypertensive and normal individuals (92.3 +/- 4.9 vs 86.5 +/- 7.3 mumol/L, p = NS). CONCLUSIONS: Patients with hypertension are glucose intolerant, hyperinsulinemic and insulin resistant compared to a group of normotensive subjects. Hypertensive patients have higher than normal fasting plasma NEFA and insulin concentrations indicating that they might lose the ability to regulate adipocyte metabolism in fasting state.

Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy.

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.

Resistance to insulin-mediated glucose uptake and hyperinsulinemia in women who had preeclampsia during pregnancy.

Plasma glucose and insulin responses to a 75-g oral glucose load, and the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations after an infusion of somatostatin, insulin, and glucose, were determined 2 months after delivery in 26 women; 13 who had a normal pregnancy and 13 who developed preeclampsia. The plasma glucose response to oral glucose was not different in the two groups, but the plasma insulin response was significantly greater (P < .02) in those who had been preeclamptic. Although the mean (+/- SE) SSPI concentrations during the infusion study were similar in the two groups (51 +/- 2 v 56 +/- 2 microU/mL), the SSPG concentrations were significantly higher (P < .02) in those who developed preeclampsia (160 +/- 17 v 119 +/- 17 mg/dL). Thus, when studied 2 months after delivery, women who developed preeclampsia were relatively insulin resistant and hyperinsulinemic when compared to those who had an uncomplicated pregnancy.

Relationship between hepatic glucose production and fasting plasma glucose concentration in patients with NIDDM.

This study was initiated to reevaluate the changes in basal hepatic glucose production (HGP) rate that occur in patients with non-insulin-dependent diabetes mellitus (NIDDM). Measurements were made in 51 volunteers: 18 with normal glucose tolerance and 33 with newly diagnosed NIDDM of varying degrees of severity. To avoid the methodological problems associated with quantifying HGP over short time periods, using non-steady-state isotopic kinetics, radiolabeled glucose was infused for a 12-h period, from 10 P.M. to 10 A.M. with HGP quantified from 9 to 10 A.M.. The results showed that fasting plasma glucose (FPG) concentration and HGP were significantly correlated (r = 0.68, P < 0.001) in patients with NIDDM. However, when the 33 patients with NIDDM were divided into three groups of 11 each on the basis of FPG concentration, it became clear that the relationship between FPG and HGP was complex. Thus, values for HGP in patients with NIDDM and FPG < 180 mg/dl were not higher than in the normal population (1.67 +/- 0.07 vs. 1.69 +/- 0.04 mg.kg-1.min-1, NS). Significant increases (P < 0.01) in HGP above normal were seen in the 11 patients with NIDDM and FPG concentrations between 180 and 250 mg/dl (2.05 +/- 0.07 mg.kg-1.min-1), as well as in those with FPG > 250 mg/dl (2.18 +/- 0.13 mg.kg-1.min-1). Although those with the highest FPG concentrations tended to have the greatest values for HGP, the difference between the latter two groups of patients with NIDDM was not statistically significant. Finally, HGP rates in the 11 patients with FPG concentrations > 250 mg/dl were only 29% higher than values in the control population.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic insulin extraction and insulin clearance in patients with essential hypertension.

To understand the mechanism of hyperinsulinemia in patients with high blood pressure, we studied 20 untreated essential hypertensives and 20 age, sex and body mass index-matched normotensive control subjects. C-peptide concentrations and C-peptide to insulin molar ratio in response to a 75 g oral glucose challenge were used to evaluate the beta cells function and for calculation of hepatic extraction of insulin. Modified insulin suppression test was employed to compared the insulin-stimulated glucose uptake and insulin clearance rate between two groups. Patients with hypertension had significantly higher plasma glucose, insulin and C-peptide responses as compared to normal subjects (P < 0.05, p < 0.01, and P < 0.03, respectively). Mean steady state plasma glucose (SSPG) concentrations were also higher in hypertensive group than normotensive group (11.5 +/- 1.4 vs 6.7 +/- 0.9 mmol/L, p < 0.01) despite that mean steady state plasma insulin (SSPI) values were relatively similar, indicating the presence of insulin resistance. Hepatic insulin extraction was found to be elevated in patients with high blood pressure when compared to normal subjects (82 +/- 3 vs 72 +/- 2%, p < 0.05). However, there were no difference in insulin clearance rate between two groups (592 +/- 38 vs 559 +/- 40 mL/m2/min, p = NS). In conclusion, hyperinsulinemia in patients with hypertension result from hypersecretion of beta cells and increased hepatic extraction of insulin. No difference was found in insulin clearance rate between hypertensive and normotensive subjects.

Prospective evaluation of insulin resistance and lipid metabolism in women receiving oral contraceptives.

OBJECTIVES: It has been suggested that normal women receiving oral contraceptives (OC) may develop a series of metabolic side-effects which relate to the risk of cardiovascular disease. These metabolic disturbances include changes in glucose and insulin metabolism, raised serum lipid and lipoprotein concentrations and elevated blood pressure. All these changes indicate that OC might cause insulin resistance. We have prospectively examined the effect of OC on insulin resistance and lipid metabolism including Lp(a) values. PATIENTS: The study group comprised 13 normally menstruating Chinese women. DESIGN: The study subjects were given a combined triphasic oral contraceptive which was administered on a 21-day on, 7-day off medication cyclic regimen, the first pill being administered on day 5 from the beginning of menses. The metabolic investigations were carried out during luteal phase before OC and again the third week of the third month of OC administration. MEASUREMENTS: Metabolic evaluation including insulin secretion and insulin-mediated glucose uptake were evaluated by oral glucose tolerance test and the modification of insulin suppression test. Fasting triglyceride, cholesterol, HDL-cholesterol and Lp(a) concentrations were also measured. RESULTS: The plasma glucose and insulin responses during a 75-g oral glucose challenge increased significantly (P < 0.05 and P < 0.03, respectively). The steady-state plasma glucose (SSPG) concentrations achieved during constant infusion of glucose, insulin and somatostatin increased significantly after 3 cycles of OC administration (glucose 7.5 +/- 0.8 vs 12.4 +/- 0.7 mmol/l, P < 0.001) while the steady-state plasma insulin (SSPI) concentrations were relatively similar (410 +/- 14 vs 391 +/- 7 pmol/l, NS). Plasma triglyceride levels increased significantly (0.81 +/- 0.12 vs 1.09 +/- 0.19 mmol/l, P < 0.03) following OC administration. Fasting plasma cholesterol, HDL cholesterol and calculated LDL cholesterol concentrations did not change as compared with baseline values, nor did the ratio of total cholesterol to HDL cholesterol. The Lp(a) concentrations did not change during the administration of OC (81 +/- 25 vs 71 +/- 21 mg/l, NS). CONCLUSIONS: These data indicated that intake of OC for 3 cycles induced glucose intolerance, hyperinsulinaemia and insulin resistance in normal menstruating Chinese women. These changes occurred in association with elevated plasma triglyceride concentrations and no alteration in Lp(a) or other lipid values.

PIP: In Taipei, Taiwan, physicians started 13 normally menstruating women on an isocaloric diet (30 kcal/kg; 50% carbohydrate, 30% fat, and 20% protein) and administered a combined triphasic oral contraceptive (OC) to evaluate the effect of the OC on insulin resistance and lipid metabolism including Lp(a) values. (Lp(a) levels may be a risk factor for coronary heart disease.) After three months of taking OCs, the plasma glucose concentration increased significantly (p 0.05). The plasma insulin response to oral glucose was also significantly higher than before OC use (p 0.03). The steady state plasma glucose concentration during constant infusion of glucose, insulin, and somatostatin was much higher three months after OC administration than before OC administration (12.4 vs. 7.5 mmol/l; p 0.001). After three cycles of OC use, the only fasting plasma lipoprotein that increased significantly was triglyceride (0.81 vs. 1.09 mmol/l; p 0.03). The Lp (a) levels stayed essentially the same. OC use decreased significantly the concentration of all serum steroids except DHEAS. These findings indicate that administration of a triphasic low dose OC for three cycles caused glucose intolerance, hyperinsulinemia, and insulin resistance in normal women. It also raised plasma triglyceride concentrations, but did not affect Lp(a) and other lipid values.

Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism in patients with hypercholesterolemia.

Treatment of patients with type IIA hyperlipoproteinemia (HLP) with pravastatin for 3 months led to significant decreases (p < 0.001) in total cholesterol (7.18 +/- 0.30 to 5.75 +/- 0.30 mmol/L), LDL cholesterol (5.56 +/- 0.33 to 4.02 +/- 0.32 mmol/L), and ratio of total cholesterol to HDL cholesterol (6.5 +/- 0.4 to 4.6 +/- 0.4). Decreases of a similar magnitude were also seen in patients with type IIB HLP. Plasma glucose and insulin concentrations after an oral glucose load and from 8 AM to 4PM in response to meals were higher in patients with Type IIB HLP, who also had higher steady-state plasma glucose concentrations after an infusion of somatostatin, insulin, and glucose (12.4 +/- 1 vs 5.5 +/- 0.8 mmol/L, p < 0.001). Because steady-state plasma insulin concentrations were similar in both groups, patients with type IIB HLP were relatively insulin resistant. Furthermore, day-long plasma glucose concentrations and insulin resistance were modestly, but significantly (p < 0.01), greater after treatment in both groups. In conclusion, LDL cholesterol metabolism improved in hypercholesterolemic subjects treated with pravastatin, but the hypertriglyceridemia, insulin resistance, relative glucose intolerance, and hyperinsulinemia present in patients with type IIB HLP either did not improve with treatment or was somewhat worse.

Insulin resistance, glucose intolerance, and hyperinsulinemia in patients with microvascular angina.

Plasma glucose and insulin responses to oral glucose and insulin-mediated glucose disposal were determined in 20 patients with microvascular angina and 20 normal volunteers who were similar in terms of age, gender distribution, and degree of obesity. Plasma glucose and insulin responses to a 75-g oral glucose challenge were significantly higher in those with microvascular angina (P < .001), as were steady-state plasma glucose concentrations after a 180-minute infusion of somatostatin, glucose, and insulin (12.2 +/- 1.0 v 7.6 +/- 0.6 mmol/L, P < .001). Since steady-state plasma insulin concentrations were similar in the two groups (627 +/- 32 v 631 +/- 29 pmol/L), these data indicate that patients with microvascular angina are insulin-resistant, glucose-intolerant, and hyperinsulinemic compared with a matched group of normal volunteers.

Effect of nicardipine treatment on carbohydrate and lipoprotein metabolism in patients with hypertension.

This study evaluated the effect of nicardipine, calcium channel blocker, monotherapy on blood pressure and metabolic changes. Various aspect of carbohydrate and lipoprotein metabolism were studied before and after 12 weeks of nicardipine treatment in 23 patients with mild to moderate essential hypertension. Nicardipine was well tolerated and induced a significant decrease (p < 0.001) in both systolic and diastolic blood pressure without any changes in heart rate. Plasma levels of fasting glucose, insulin, C-peptide and hemoglobin A1c, hepatic extraction of insulin were similar following nicardipine treatment. Plasma glucose and insulin responses to an oral glucose challenge did not change in association with nicardipine therapy. Although high density lipoprotein (HDL) cholesterol concentration increased slightly, it did not reach statistical significance. Total cholesterol and low density lipoprotein (LDL) cholesterol levels also increased insignificantly. LDL triglyceride and very low density lipoprotein (VLDL) triglyceride concentrations were higher marginally, which resulted in slightly but insignificantly increase in total triglyceride concentration in association with nicardipine monotherapy for 12 weeks. In conclusion, treatment of patients with mild to moderate hypertension with nicardipine led to lower blood pressure effectively while had no significant influence on carbohydrate and lipoprotein metabolism.

Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia.

Plasma glucose and insulin responses to oral glucose and mixed meals and the ability of insulin to stimulate glucose disposal were quantified in normal volunteer subjects and patients with types IIA, IIB, and IV hyperlipoproteinemia (HLP). The results indicated that patients with either type IIB or IV HLP had higher plasma glucose (p < 0.05-< 0.001) and insulin (p < 0.001) responses to both oral glucose and mixed meals compared with the normal subjects and patients with type IIA HLP. Steady-state plasma glucose concentrations (mmol/L) were also higher (p < 0.001) in patients with types IIB (13.3 +/- 0.6) and IV (12.8 +/- 1.2) HLP during a continuous infusion of somatostatin, glucose, and insulin than either the control group (volunteer subjects) (6.2 +/- 0.9) or patients with type IIA HLP (5.6 +/- 1.0). Because the steady-state plasma insulin concentrations were similar in all four groups, patients with either type IIB or IV HLP were resistant to insulin-mediated glucose uptake. These data indicate that patients with hypertriglyceridemia are insulin resistant, glucose intolerant, and hyperinsulinemic, irrespective of the plasma cholesterol concentration. The results further demonstrate that hypercholesterolemic patients with normal triglyceride concentrations do not have any abnormalities of glucose and insulin metabolism.

Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension.

The metabolic changes associated with doxazosin treatment of hypertension were evaluated in ten patients with mild hypertension (mean +/- SEM = 150 +/- 3/100 +/- 1 mm Hg) and a plasma triglyceride (TG) concentration > 1.50 mmol/L. The blood pressure was lower after 4 to 6 months of doxazosin treatment (mean +/- SEM = 134 +/- 4/87 +/- 1 mm Hg), which was also associated with a significantly lower plasma insulin response to a 75 g oral glucose load, and lower plasma TG and cholesterol concentrations. In addition, insulin-mediated glucose uptake was significantly greater after doxazosin treatment. These data suggest that doxazosin treatment of patients with mild hypertension is associated with changes in insulin and lipid metabolism that should decrease the risk of coronary heart disease.