Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes

Aim

Altered adipokine serum concentrations early reflect impaired adipose tissue function in obese patients with type 2 diabetes (T2D). It is not entirely clear whether these adipokine alterations are already present in prediabetic states and so far there is no comprehensive adipokine panel available. Therefore, the aim of this study was to assess distinct adipokine profiles in patients with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or T2D.

Methods

Based on 75 g oral glucose tolerance tests, 124 individuals were divided into groups of IFG (n = 35), IGT (n = 45), or NGT (n = 43). Furthermore, 56 subjects with T2D were included. Serum concentrations of adiponectin, chemerin, fetuin-A, leptin, interleukin (IL)-6, retinol-binding protein 4 (RBP4), monocyte chemoattractant protein (MCP)-1, vaspin, progranulin, and soluble leptin receptor (sOBR) were measured by ELISAs.

Results

Chemerin, progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum concentrations were differentially regulated among the four investigated groups but only circulating chemerin was significantly different in patients with IGT compared to those with IFG. Compared to T2D the IFG subjects had higher serum chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the comparison of the T2D and IGT group.

Conclusion

Alterations in adipokine serum concentrations are already detectable in prediabetic states, mainly for chemerin, and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D development. In addition, distinct adipokine serum patterns in individuals with IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of these prediabetic states.     

Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance

Glucose tolerance declines with age, resulting in a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Hyperglycemia per se can lead to impaired beta-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related beta-cell dysfunction in older people (65 +/- 8 yr) with IGT treated with the alpha-glucosidase inhibitor acarbose (n = 14) or placebo (n = 13) for 6 wk in a randomized, double-blind study. Baseline and posttreatment studies included 1) an oral glucose tolerance test (OGTT), 2) 1-h postprandial glucose monitoring, 3) a frequently sampled intravenous glucose tolerance test (insulin sensitivity, or S(I)), and 4) glucose ramp clamp (insulin secretion rates, or ISR), in which a variable glucose infusion increases plasma glucose from 5 to 10 mM. The treatment groups had similar baseline body mass index; fasting, 2-h OGTT, and 1-h postprandial glucose levels; and S(I). In these carefully matched older people with IGT, both fasting (5.7 +/- 0.2 vs. 6.3 +/- 0.2 mM, P = 0.002) and 1-h postprandial glucose levels (6.9 +/- 0.3 vs. 8.2 +/- 0.4 mM, P = 0.02) were significantly lower in the acarbose than in the placebo group. Despite this reduction of chronic hyperglycemia in the acarbose vs. placebo group, measures of insulin secretion (ISR area under the curve: 728 +/- 55 vs. 835 +/- 81 pmol/kg, P = 0.9) and acute insulin response to intravenous glucose (329 +/- 67 vs. 301 +/- 54 pM, P = 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse beta-cell dysfunction in older people with IGT.     

Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance

The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate beta-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 +/- 0.18, P = 0.004] amounted to 18 +/- 2 nmol/m(2) (32 +/- 4% of oral response), and its time course matched that of total insulin secretion. The beta-cell glucose sensitivity (OGTT/IV ratio = 1.52 +/- 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 +/- 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, beta-cell glucose sensitivity (75 +/- 14 vs. 156 +/- 28 pmol.min(-1).m(-2).mM(-1) of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of beta-cell glucose sensitivity (OGTT/IV ratio = 1.73 +/- 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of beta-cell function, particularly beta-cell glucose sensitivity. In IGT, beta-cell function is inherently impaired, whereas the incretin effect is only partially affected.     

Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test

The utility of the disposition index as a measure of beta-cell compensatory capacity rests on the established hyperbolic relationship between its component insulin secretion and sensitivity measures as derived from the intravenous glucose tolerance test (IVGTT). If one is to derive an analogous measure of beta-cell compensation from the oral glucose tolerance test (OGTT), it is thus necessary to first establish the existence of this hyperbolic relationship between OGTT-based measures of insulin secretion and insulin sensitivity. In this context, we tested five OGTT-based measures of secretion (insulinogenic index, Stumvoll first phase, Stumvoll second phase, ratio of total area-under-the-insulin-curve to area-under-the-glucose-curve (AUC(ins/gluc)), and incremental AUC(ins/gluc)) with two measures of sensitivity (Matsuda index and 1/Homeostasis Model of Assessment for insulin resistance (HOMA-IR)). Using a model of log(secretion measure) = constant + beta x log(sensitivity measure), a hyperbolic relationship can be established if beta is approximately equal to -1, with 95% confidence interval (CI) excluding 0. In 277 women with normal glucose tolerance (NGT), the pairing of total AUC(ins/gluc) and Matsuda index was the only combination that satisfied these criteria (beta = -0.99, 95% CI (-1.66, -0.33)). This pairing also satisfied hyperbolic criteria in 53 women with impaired glucose tolerance (IGT) (beta = -1.02, (-1.72, -0.32)). In a separate data set, this pairing yielded distinct hyperbolae for NGT (n = 245) (beta = -0.99, (-1.67, -0.32)), IGT (n = 116) (beta = -1.18, (-1.84, -0.53)), and diabetes (n = 43) (beta = -1.37, (-2.46, -0.29)). Moreover, the product of AUC(ins/gluc) and Matsuda index progressively decreased from NGT (212) to IGT (193) to diabetes (104) (P < 0.001), consistent with declining beta-cell function. In summary, a hyperbolic relationship can be demonstrated between OGTT-derived AUC(ins/gluc) and Matsuda index across a range of glucose tolerance. Based on these findings, the product of these two indices emerges as a potential OGTT-based measure of beta-cell function.     

Concentrated loss of insulin secretion in Wistar rats with normal glucose tolerance

Rats with decreased insulin response and with normal glucose tolerance were concentrated by repeated selective breeding of normal Wistar rats with low insulinogenic index. In general, the mean insulinogenic index of the inbred offsprings showed a tendency to decrease more than their parents generation. Thus mean insulinogenic indices in second (F2), third (F3) and fourth (F4) generations were significantly reduced more than the normal rats without glucose intolerance. Pancreatic islets from the F3 and F4 rats lost partially their ability to release insulin at 20 mM glucose in vitro. It is suggested that a defect responsible for the decreased insulin response in the F2, F3 and F4 rats resulted from a loss of the ability to secrete insulin in each islet, and that this defect was concentrated by repeated selective breeding of normal Wistar rats.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

Background

Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients.

Methods

We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.

Results

A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).

Conclusions

In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

ABSTRACT: BACKGROUND: Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals. METHODS: Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group ([MINUS SIGN]21.19 % [PLUS-MINUS SIGN] 17.90 %; P < 0.001) and the OG group ([MINUS SIGN]17.59 % [PLUS-MINUS SIGN] 26.64 %) than in the control group (6.46 % [PLUS-MINUS SIGN] 9.17 %; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group ([MINUS SIGN]18.91 % [PLUS-MINUS SIGN] 16.58 %) than in the control group (6.78 % [PLUS-MINUS SIGN] 11.43 %; P < 0.001) or the TM group (5.22 % [PLUS-MINUS SIGN] 37.22 %; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = [MINUS SIGN]0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = [MINUS SIGN]0.462; P < 0.05) and the AUC of IRI (r = [MINUS SIGN]0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables. CONCLUSION: Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.     

Factors responsible for glucose intolerance in Japanese subjects with impaired fasting glucose.

Impaired fasting glucose (IFG) represents risk of development of diabetes (DM) and its complications. We investigated insulin secretion and insulin sensitivity in 403 IFG subjects divided into three levels of 2-hour postchallenge glucose (2-h PG) to clarify the factors responsible in the development of glucose intolerance in Japanese IFG. Nearly 60% of the subjects at annual medical check-up with FPG of 6.1-7.0 mmol/l at the first screening were diagnosed by 75 g oral glucose tolerance test (OGTT) to have impaired glucose tolerance (IGT; FPG <7.0 mmol/l and 7.8 mmol/l <2-h PG <11.1 mmol/l) or DM (isolated postchallenge hyperglycemia (IPH); FPG <7.0 mmol/l and 11.1 mmol/l <2-h PG level). The primary factor in the decreased glucose tolerance was a decrease in early-phase insulin, with some contribution of increasing insulin resistance. In addition, IFG/IGT and IFG/IPH subjects showed a compensatory increase in basal insulin secretion sufficient to keep FPG levels within the non-diabetic range. IFG is composed of three different categories in basal, early-phase insulin secretion, and insulin sensitivity.     

Postexercise dose-response relationship between plasma glucose and insulin secretion

To investigate whether exertion changes beta-cell reactivity to glucose stimulation and to characterize the beta-cell response to glucose in humans, we performed four sequential 90-min hyperglycemic clamps (7, 11, 20, and 35 mM). Concentrations of hormones and metabolites involved in glucoregulation were measured. Metabolic rate and substrate utilization were studied by indirect calorimetry. Studies were performed without prior exercise, as well as 2 and 48 h after 60 min of bicycle exercise at 150 W. We found 1) a progressive increase in insulin concentrations reaching 1,092 +/- 135 microU/ml with increasing glucose levels, 2) linear relationships between glucose concentrations and concentrations of C-peptide (r = 0.931 +/- 0.008) and proinsulin (r = 0.952 +/- 0.009),3) increased glucose oxidation with increasing glucose uptake, 4) increased plasma norepinephrine, O2 uptake, and beta-hydroxybutyrate at greater than or equal to 20 mM glucose, and 5) no change in beta-cell response or glucose-induced thermogenesis after one bout of exercise despite no compensating changes in plasma concentrations of hormones or metabolites. We conclude that the beta-cell has a very large secretory potential. Secretion of the beta-cell increases linearly with prolonged, graded hyperglycemia. The processing of proinsulin is unchanged during prolonged beta-cell stimulation. In addition, hyperglycemia and sympathetic nervous activity induced by hyperinsulinemia enhance metabolic rate and ketone body production. Finally, a single bout of exercise does not influence either the beta-cell response to intravenous glucose or glucose-induced thermogenesis.     

The relationship between maximal oxygen uptake and glucose tolerance/insulin response ratio in normal young men.

Maximal oxygen uptake (VO2max.), glucose tolerance (K-value), and insulin response (IRI-area) were studied in seventeen young, non-obese, non-diabetic males. The ratio between K-value and IRI-area correlated significantly with VO2 max. (r = 0.70, p less than 0.01) also when differences in body fat mass were eliminated by partial correlation analysis (r = 0.56, p less than 0.05). Subjects with a high VO2 max. thus maintained a given glucose tolerance with a lower insulin response than did subjects in whom VO2 max. was low.     

Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance

Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C-peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced.     

Intravenous glucose tolerance, insulin response to glucose, peripheral sensitivity to insulin, and serum lipoproteins in post-myocardial infarct patients with normal fasting blood glucose

Intravenous glucose tolerance (IVGTT), basal insulin and insulin response to glucose infusion (GIT), insulin sensitivity, and lipoprotein patterns were determined in non-obese post-coronary subjects, 3-6 months after myocardial infarction. Twelve had decreased and 31 normal IVGTT. The control group comprised 31 subjects with normal IVGTT, who did not display any signs of coronary disease. The post-coronary patients were not taking any drugs except for furosamide, which was shown not to influence insulin response to GIT or glucose tolerance. Decreased IVGTT in the post-coronary patients could be ascribed to decreased insulin response and insulin resistance. These two derangements are considered as hereditary markers in glucose intolerance and type 2 diabetes. Accordingly, our findings suggest that glucose intolerance in subjects with myocardial infarcts has the same background. The post-coronary patients demonstrated elevated triglycerides (TG) and cholesterol in total serum and in very low density lipoproteins (VLDL), the lipoprotein patterns being almost identical in post-coronary patients with or without decreased IVGTT. No relationship was found in the control and post-coronary groups between IVGTT, basal insulin, stimulated insulin (KI, IP), and insulin sensitivity (KG), on the one hand, and total or VLDL TG or any other lipoprotein particle, on the other. Thus, the derangements in glucose, insulin, and serum triglyceride metabolism were independent abnormalities (risk factors) in these non-obese post-coronary patients.     

Soluble CD40 ligand levels in otherwise healthy subjects with impaired fasting glucose

Unlike diabetes mellitus and impaired glucose tolerance, it is not clear whether the subjects with impaired fasting glucose (IFG) are at increased risk of atherosclerosis and cardiovascular diseases. The CD40-CD40 ligand interaction is involved in the mechanism of atherosclerosis. We investigated whether soluble CD40L (sCD40L) as well as high sensitive C-reactive protein (hsCRP) levels are increased in subjects with IFG having no confounding factors for inflammation or atherosclerosis. Twenty four IFG subjects with no additional disorders and 40 appropriate healthy controls were studied. sCD40L and hsCRP levels in the IFG and control groups were similar. Blood pressures, total and LDL-cholesterol, and triglyceride levels were also similar, whereas HDL-cholesterol was lower and HOMA-IR indexes were higher in the IFG group. Though the sample size was small, the present data show that sCD40L seems not to alter in subjects with IFG suggesting that it might not be an independent risk factor for atherosclerosis.     

Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance

Background

Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects.

Methods

Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day) or the cilostazol group (100–200 mg/day) in this international, 2-year, prospective follow-up interventional study.

Results

The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index.

Conclusion

This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.     

First phase release coefficient of insulin in subjects with normal glucose tolerance on glucose infusion analyzed by computer simulation

We report here a mathematical model using computer simulation to solve the phase fractionation coefficient (f) of instantaneous insulin release on glucose infusion. By extensive model testing with the cited parameters obtained from the literature, the values of the factor f were shown to lie in range of 0.93+/-0.02 (mean+/-2S.D., n=15), indicating that the high pulsatile bolus of glucose by i.v. infusion may trigger acute insulin release (AIR) corresponding to a fraction of more than 90% of the stored insulin release in the first phase from the secretory granules of pancreatic beta cells. In addition, the value of the factor f was shown to be independent of both the glucose infusion method and the non-insulin-dependent uptake of glucose.     

Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance.

Background

Left ventricular hypertrophy (LVH) is a powerful independent risk factor for cardiovascular morbidity and mortality among hypertensive patients. Data regarding relationships between diabetes and LVH are controversial and inconclusive, whereas possible gender differences were not specifically investigated. The goal of this work was to investigate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes.

Methods

Five hundred fifty hypertensive patients with at least one additional cardiovascular risk factor (314 men and 246 women, age 52 to 81, mean 66 ± 6 years), were enrolled in the present analysis. In 200 (36%) of them – 108 men and 92 women – type 2 diabetes mellitus was found upon enrollment. End-diastolic measurements of interventricular septal thickness (IVS), LV internal diameter, and posterior wall thickness were performed employing two-dimensionally guided M-mode echocardiograms. LVH was diagnosed when LV mass index (LVMI) was >134 g/m² in men and >110 g/m² in women.

Results

Mean LVMI was significantly higher among diabetic vs. nondiabetic women (112.5 ± 29 vs. 105.6 ± 24, p = 0.03). In addition, diabetic women presented a significantly higher prevalence of increased IVS thickness, LVMI and left atrial diameter on intra-gender comparisons. The age adjusted relative risk for increased LVMI in diabetics vs. nondiabetics was 1.47 (95% CI: 1.0–2.2) in females and only 0.8 (0.5–1.3) in males.

Conclusion

Type 2 diabetes mellitus was associated with a significantly higher prevalence of LVH and left atrial enlargement in hypertensive women.     

Relationship between serum concentrations of interleukin-6 and tumor necrosis factor alpha in female Turkish subjects with normal and impaired glucose tolerance.

Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) concentrations were measured in subjects during two-hour glucose loading in order to investigate the effects of glucose on serum IL-6 and TNFalpha concentrations. Twenty-six female subjects (mean age 60 +/- 10 years) had normal glucose tolerance (NGT) and nineteen female subjects (mean age: 63 +/- 9 years) had impaired glucose tolerance (IGT) according to WHO criteria. Serum IL-6 and TNFalpha concentrations were measured by chemiluminescent immunometric assay. Subjects with IGT have higher fasting serum TNFalpha levels than subjects with NGT (p < 0.01). Serum IL-6 and TNFalpha concentrations were elevated during glucose loading (for each comparison, p < 0.01). The increase in serum TNFalpha concentrations in IGT was greater than in NGT (p < 0.01). Serum IL-6 and TNFalpha concentration significantly correlated with insulin and glucose in IGT group (for each comparison, p < 0.01). The correlation between serum glucose and cytokines concentrations was significant in IGT (for each comparison, p < 0.01). There was also a positive correlation between serum IL-6 and TNFalpha in NGT and IGT (for each comparison, p < 0.01). In conclusion, hyperglycemia is associated with increased circulating cytokine concentrations and fasting TNFalpha concentrations seem to be more associated with IGT than IL-6.     

Hormone replacement therapy decreases insulin resistance and lipid metabolism in Japanese postmenopausal women with impaired and normal glucose tolerance

OBJECTS: To investigate the effect of combined estrogen and progesterone therapy on insulin resistance (IR) and carbohydrate and lipid metabolism in postmenopausal women (PMW) with impaired (IGT) and normal glucose tolerance (NGT). METHODS: Sixteen Japanese PMW with IGT and 33 with NGT received daily oral hormone replacement therapy (HRT; 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate) for 12 months. As controls, 13 Japanese PMW with IGT and 31 with NGT were enrolled and not treated by HRT. Fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI), and IR were measured in each subject at study initiation and 12 months later. We used homeostasis model assessment (HOMA) to determine IR. RESULTS: FPG and HOMA IR were decreased in both HRT groups, and fasting IRI was reduced in the HRT-NGT group. In controls, FPG, fasting IRI, and HOMA IR were unaltered. Total and low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased in both HRT groups, but triglyceride was unchanged. In controls, lipid metabolism was unaltered. CONCLUSION: HRT decreased IR and improved carbohydrate and lipid metabolism in Japanese PMW with IGT and NGT. These beneficial effects argue for the use of HRT in PMW with IGT as well as NGT.