OBJECTIVE -To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA 1c , fasting plasma glucose (FPG), and mealtime glucose excursions.RESEARCH DESIGN AND METHODS -In this randomized double-blind study, patients with an HbA 1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA 1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.RESULTS -At study end point, HbA 1c was reduced from baseline with nateglinide and metformin but was increased with placebo (Ϫ0.5, Ϫ0.8, and ϩ0.5%, respectively; P Յ 0.0001). Changes in FPG followed the same pattern (Ϫ0.7, Ϫ1.6, and ϩ0.4 mmol/l; P Յ 0.0001). Combination therapy was additive (HbA 1c Ϫ1.4% and FPG Ϫ2.4 mmol/l; P Յ 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC] 0-130min Ϫ2.1, Ϫ1.1, and Ϫ0.6 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001). An even greater effect was observed with combination therapy (AUC 0-130min Ϫ2.5 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001 vs. metformin and placebo). All regimens were well tolerated.CONCLUSIONS -Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA 1c , FPG, and postprandial hyperglycemia.

Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension.

Resistance to insulin-mediated glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin-dependent diabetes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following five experimental groups: normal blood pressure, nonobese (n=17); normal blood pressure, obese (n=18); high blood pressure, nonobese (n=18); high blood pressure, obese (n=19); and high blood pressure, obese, noninsulin-dependent diabetes mellitus (n=16). Plasma glucose and insulin concentrations were measured before and after a 75-g oral glucose load. Resistance to insulin-mediated glucose disposal was estimated by determining the steady-state plasma insulin and glucose concentrations during the last 30 minutes of a continuous infusion of somatostatin (5 jug/min), exogenous insulin (25 mU/m 2 per minute), and glucose (240 mg/m 2 per minute). Since the steady-state plasma insulin concentrations I n the past several years it has become apparent that the ability of insulin to stimulate glucose disposal can vary widely from person to person. 12 In addition, it has also been shown 3 -8 that insulin resistance is a common feature in patients who are obese or have either hypertension or non-insulin-dependent diabetes mellitus (NIDDM). Patients with high blood pressure and/or NIDDM tend to be overweight, and it has been suggested that obesity plays a central role in the development of insulin resistance and its associated abnormalities.9 ' 10 Thus, obesity can be viewed as the cause of insulin resistance in patients with high blood pressure and/or NIDDM or simply as a factor that modulates insulin-mediated glucose disposal in any individual, thereby making that individual more likely to develop hypertension or NIDDM. We initiated the present study to address these issues. MethodsThis study was performed in 88 volunteers in good general health with the exception of hypertension with or without the codiagnosis of NIDDM. Subjects were recruited to create the following five experimental groups: (1) are similar in all subjects, the higher the steady-state plasma glucose, the more insulin resistant the individual. Nonobese subjects with normal blood pressure had the lowest plasma glucose and insulin responses and steady-state plasma glucose concentrations, and their values were significantly different from the other four groups. Obese or nonobese subjects with high blood pressure had significantly higher plasma glucose responses and steady-state plasma glucose concentrations than did their respective weight-matched control subjects. Finally, plasma glucose responses and steady-state plasma glucose concentrations were significantly higher in obese subjects with both high blood pressure and non-insulin-dependent diabetes mellitus. These results support the view that the effects of obesity, high...

This community mail-based survey received responses from 665 women to questions in three areas: (1) sources of information about menopause, (2) knowledge of health risks associated with menopause, and (3) knowledge about hormone replacement therapy (HRT). Women received information from many sources, including healthcare providers, friends, and mothers, but the number one source of information about menopause was women's magazines (76%). Over half of women surveyed said they had left healthcare appointments with unanswered questions about menopause and HRT. Although women seemed to have a basic understanding of the symptoms of menopause, their knowledge of the long-term health risks affected by menopause was poor. For example, women were much more likely (60%) to know that osteoporosis risk increased with menopause than to know that heart disease risk increased (30%) despite the much higher prevalence and severity of heart disease as a health problem of menopausal women. Many women thought that menopause itself (independent of aging) increased the risk of breast cancer. This finding may help explain the low percentage of women who take HRT for menopause despite proven health benefits. It is clear that better education about menopause needs to be accomplished regarding the long-term risk associated with menopause and the pros and cons of HRT. Strategies for improving education and interactions with healthcare providers are suggested.

Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)