Insulin Response Curve Research Articles

Interaction of fish oil and a glucocorticoid on metabolic responses to an oral glucose load in healthy human subjects

Compared with saturated fat, n-3 long-chain PUFA-rich fish oil improves insulin sensitivity in rats. We studied whether n-3 long-chain PUFA could prevent insulin resistance induced by dexamethasone (a glucocorticoid) in healthy human volunteers. A group of eight subjects was studied twice after a 2 d dexamethasone treatment, before and after a 3-week supplementation with fish oil (providing daily doses of 1.1 g 20 : 5n-3 and 0.7 g 22 : 6n-3). The subjects were studied during the basal state and over the 6 h following an oral glucose load (1 g/kg). Plasma glucose fluxes were traced with [6,6-2H2]glucose and [13C]glucose (naturally 13C-enriched corn glucose). Substrate oxidation was obtained from indirect calorimetry. Following fish oil supplementation, plasma glucose fluxes and substrate oxidation were maintained despite a 17 % reduction (P<0.05) in the area under the curve of plasma insulin response, suggesting an insulin-sensitizing effect.

Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) has been shown to cause a reduction in quality of life. This study examines the extent of different PCOS symptoms on quality-of-life, psychosocial well-being and sexual satisfaction. Complete metabolic, hormonal, clinical and psychosocial data were obtained from a total of 120 women with PCOS. Patients were compared with 50 healthy women to establish reductions in quality-of-life and emotional well-being. In addition, the correlation between psychosocial variables and the major clinical PCOS features obesity (body mass index (BMI)), excessive body hair (hirsutism score), acne, hyperandrogenism (serum testosterone levels), disturbed insulin regulation (area under the insulin response curve and homeostasis model assessment of insulin resistance), menstrual cycle disturbances and infertility were analyzed. PCOS patients showed significant reductions in quality-of-life, increased psychological disturbances, and decreased sexual satisfaction when compared with healthy controls. BMI and hirsutism scores, but not the presence of acne, were associated with physical aspects of quality-of-life and sexual satisfaction. No clear effect of androgens or insulin resistance on psychosocial variables was detected. Similarly, the type of menstrual cycle disturbances or infertility had no impact on psychological well-being. In PCOS, changes in appearance, particularly obesity and hirsutism, reduce physical dimensions of quality-of-life and decrease sexual satisfaction. The role of biochemical, endocrine and metabolic parameters as well as menstrual irregularities and infertility appeared to be less important. Clinicians should pay attention to the psychosocial dimensions of PCOS on an individual basis, regardless of symptom severity or treatment response.

Protein Ingestion Prior to Strength Exercise Affects Blood Hormones and Metabolism

The effects of protein consumption before strength training session on blood hormones, energy metabolites, RER, and excess postexercise oxygen consumption (EPOC) were examined. Ten resistance-trained young men consumed either a 25 g of whey and caseinate proteins (PROT) or a noncaloric placebo (P) in a liquid form 30 min before a heavy strength training session (STS) in a crossover design separated by at least 7 d. STS lasted 50 min and included 5 x 1 RM squats, 3 x 10 RM squats and 4 x 10 RM leg presses with 2-, 3-, and 2-min recoveries, respectively. A protein-carbohydrate supplement was consumed after STS in both trials. Venous blood samples were collected before, during, and after STS and oxygen consumption before and after STS. Serum growth hormone (GH), testosterone, and free fatty acids (FFA) were significantly (P < or = 0.05) higher in P compared with PROT 5 min after an STS. The calculated area under curve (AUC) of the serum insulin response during an STS was significantly (P < 0.001) higher in PROT compared with P. The EPOC value from 90 to 120 min after an STS was significantly greater in the PROT condition compared with P (P = 0.01), and PROT treatment had a significantly higher RER 2 h postexercise (P = 0.04). The AUC of serum FFA during STS correlated significantly and negatively with RER 10-30 min after STS (r = -0.53, P = 0.02). Consuming 25 g of whey and caseinate proteins 30 min before an STS significantly decreases serum GH, testosterone, and FFA levels, and increases serum insulin during an STS. Furthermore, the pre-STS protein increased EPOC and RER significantly during 2-h recovery after STS.

Ingestion of a high-glycemic index meal increases muscle glycogen storage at rest but augments its utilization during subsequent exercise

The aim of this study was to compare the effect of preexercise breakfast containing high- and low-glycemic index (GI) carbohydrate (CHO) (2.5g CHO/kg body mass) on muscle glycogen metabolism. On two occasions, 14 days apart, seven trained men ran at 71% maximal oxygen uptake for 30 min on a treadmill. Three hours before exercise, in a randomized order, subjects consumed either isoenergetic high- (HGI) or low-GI (LGI) CHO breakfasts that provided (per 70 kg body mass) 3.43 MJ energy, 175 g CHO, 21 g protein, and 4 g fat. The incremental areas under the 3-h plasma glucose and serum insulin response curves after the HGI meal were 3.9- (P < 0.05) and 1.4-fold greater (P < 0.001), respectively, than those after the LGI meal. During the 3-h postprandial period, muscle glycogen concentration increased by 15% (P < 0.05) after the HGI meal but remained unchanged after the LGI meal. Muscle glycogen utilization during exercise was greater in the HGI (129.1 +/- 16.1 mmol/kg dry mass) compared with the LGI (87.9 +/- 15.1 mmol/kg dry mass; P < 0.01) trial. Although the LGI meal contributed less CHO to muscle glycogen synthesis in the 3-h postprandial period compared with the HGI meal, a sparing of muscle glycogen utilization during subsequent exercise was observed in the LGI trial, most likely as a result of better maintained fat oxidation.

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women1–3

Breakfast consumption is recommended, despite inconclusive evidence of health benefits. The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.

Metabolic and hormonal effects of five common African diets eaten as mixed meals: the Cameroon Study.

To evaluate glycaemic and insulinaemic index and in vitro digestibility of the five most common Cameroonian mixed meals consisting of rice+tomato soup (diet A), bean stew+plantains (B), foofoo corn+ndolé (C), yams+groundnut soup (D), and koki beans+cassava (E). Ten healthy non-obese volunteers, aged 19-31 y, with no family history of diabetes or hypertension. A 75 g oral glucose tolerance test followed by the eating of the test diets with carbohydrate content standardized to 75 g every 4 days with blood samples taken at 0, 15, 30, 60, 120 and 180 min. In vitro digestion of each diet according to Brand's protocol. Plasma glucose, cholesterol, triglyceride, insulin and C-peptide, with calculation of glycaemic and insulinaemic index defined as the area under the glucose and insulin response curve after consumption of a test food divided by the area under the curve after consumption of a control food containing the same amount of carbohydrate, and digestibility index. Glycaemic index (GI) varied from 34.1 (diet C) to 52.0% (diet E) with no statistical difference between the diets, and insulinaemic index varied significantly from 40.2% (C) to 70.9% (A) (P=0.03). The digestibility index varied from 18.9 (C) to 60.8% (A) (P<0.0001), and did not correlate with glycaemic or insulinaemic indices. However, carbohydrate content correlated with GI (r=0.83; P=0.04), digestibility index (r=-0.70; P<0.01), and insulinaemic index (r=0.91; P<0.01). Plasma C-peptide and plasma lipids showed little difference over 180 min following the ingestion of each meal. Glycaemic index of these African mixed meals are relatively low and might not be predicted by in vitro digestibility index.

Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of impaired glucose tolerance and type 2 diabetes. Recent evidence suggests that variation in the gene encoding the cysteine protease calpain-10 influences susceptibility to type 2 diabetes. The present study was undertaken to determine whether variation in this gene is associated with quantitative traits pertinent to the pathogenesis of PCOS and diabetes. We studied 212 women with PCOS (124 white of European ancestry, 57 African-American, 13 Hispanic, 13 Asian-American, and 5 Middle-Eastern). Each subject was genotyped for 3 DNA polymorphisms in the calpain-10 gene associated with type 2 diabetes (SNP-43, -19, and -63). The white and African-American subjects were examined for association of these polymorphisms with phenotypic features of PCOS and type 2 diabetes. There were not enough individuals in the other groups for similar genotype/phenotype analyses. Nineteen (9%) of the 212 women with PCOS were diabetic and were not included in the genotype/phenotype analyses. Twelve (63%) of these subjects were African-American. Phenotypic traits in nondiabetic white probands did not differ whether analyzed for each individual SNP (SNP-43, -19, -63) or haplotype combination. Nor was there association of SNP-43, -19, or -63 with any of the phenotypic features of type 2 diabetes or PCOS in nondiabetic African-Americans. However, nondiabetic African-Americans with the 112/121-haplotype combination had significantly higher insulin levels, in response to an oral glucose challenge, as reflected in the area under the insulin curve (257,021 +/- 95,384 vs. 136,240 +/- 11,468 pmol/min; P = 0.03), compared with those with other haplotypes. This finding was particularly notable because the 112/121 subjects were less obese. The difference between groups in area under the insulin response curve remained significant (P = 0.002 by analysis of covariance) after adjustment for body mass index. In addition to its association with insulin levels in African-Americans, the 112/121-haplotype combination was associated with an approximate 2-fold increase in risk of PCOS in both African-Americans and whites.

Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation.

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the long-chain fatty acid oleate (150 nmol/min, 24 h), the medium-chain fatty acid caprylate, or the solvent. Corticosterone (Cort) and norepinephrine (NE) were measured as indexes for HPA axis and sympathetic activity, respectively. Insulin sensitivity was assessed by means of an intravenous glucose tolerance test (IVGTT). Oleate infusion induced increases in plasma Cort (Delta = 13.5 +/- 3.6 microg/dl; P < 0.05) and NE (Delta = 235 +/- 76 ng/l; P < 0.05), whereas caprylate and solvent had no effect. The area under the insulin response curve to the IVGTT was larger in the oleate-treated group than in the caprylate and solvent groups (area = 220 +/- 35 vs. 112 +/- 13 and 106 +/- 8, respectively, P < 0.05). The area under the glucose response curves was comparable [area = 121 +/- 13 (oleate) vs. 135 +/- 20 (caprylate) and 96 +/- 11 (solvent)]. The results are consistent with the concept that increased portal free fatty acid is involved in the induction of visceral obesity-related insulin resistance via activation of the HPA axis and sympathetic system.

Insulin response and changes in composition of non-esterified fatty acids in blood plasma of middle-aged men following isoenergetic fatty and carbohydrate breakfasts

It was previously shown that a high plasma concentration of non-esterified fatty acids (NEFA) persisted after a fatty breakfast, but not after an isoenergetic carbohydrate breakfast, adversely affecting glucose tolerance. The higher concentration after the fatty breakfast may in part have been a result of different mobilization rates of fatty acids. This factor can be investigated as NEFA mobilized from tissues are monounsaturated to a greater extent than those deposited from a typical meal. Twenty-four middle-aged healthy Caucasian men were given oral glucose tolerance tests (OGTT), and for 28 d isoenergetic breakfasts of similar fat composition but of low (L) or moderate (M) fat content. The composition of NEFA in fasting and postprandial plasma was determined on days 1 and 29. No significant treatment differences in fasting NEFA composition occurred on day 29. During the OGTT and 0-1 h following breakfast there was an increase in plasma long-chain saturated NEFA but a decrease in monounsaturated NEFA (microg/100 microg total NEFA; P<0.001). Between 1 and 3 h following breakfast treatment differences occurred for total saturated and total monounsaturated fatty acids (microg/100 microg total NEFA; P<0.05), expressed as an increase in 18 : 1 and decreases in 16 : 0 and 17 : 0 in treatment M relative to treatment L (P<0.05). Serum insulin attained 35 and 65 mU/l in treatments M and L respectively during this period. Negative correlations were found between 16 : 0 in fasting plasma and both waist:hip circumference (P=0.0009) and insulin response curve area during OGTT (within treatment M, P=0.0001). It is concluded that a normal postprandial insulin response is associated with a rapid change in plasma saturated:monounsaturated NEFA. It is proposed that this change is the result of a variable suppression of fat mobilization, which may partly account for a large difference in postprandial total plasma NEFA between fatty and carbohydrate meals.

Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study.

To investigate the association of plasma insulin with all-cause, cardiovascular, and noncardiovascular mortality. We studied 22-year mortality data from the Helsinki Policemen Study The study population comprised 970 men, 34-64 years of age, who were free of coronary heart disease, other cardiovascular disease, and diabetes. Area under the insulin response curve (AUC insulin) during an oral glucose tolerance test was used to reflect plasma insulin levels. During the follow-up period, 276 men died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI 1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97) during the entire 22 years; adjusting for other risk factors, the HR was 1.88 (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67 (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03-5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped association was observed between insulin and noncardiovascular mortality, multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively Hyperinsulinemia was associated with increased all-cause and cardiovascular mortality in Helsinki policemen independent of other risk factors, although these associations weakened with the lengthening of the follow-up period. The association of insulin with noncardiovascular mortality was U-shaped.

Abstracts of literature

Abstracts of literature

Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.

The interpretation of conventional multivariate analyses concerning the relation of insulin to the risk of atherosclerotic disease is complex because of correlations of insulin with other risk factors. Therefore, we applied factor analysis to study the clustering of risk factors in the baseline data of the Helsinki Policemen Study (970 healthy men aged 34 to 64 years) and investigated whether these clusterings predict coronary heart disease (CHD) and stroke risk. Areas under the glucose and insulin response curves (AUC glucose and AUC insulin) were used to reflect glucose and insulin levels during oral glucose tolerance tests. During the 22-year follow-up, 164 men had a CHD event, and 70 men had a stroke. Factor analysis of 10 risk factor variables produced 3 underlying factors: insulin resistance factor (comprising body mass index, subscapular skinfold, AUC insulin, AUC glucose, maximal O(2) uptake, mean blood pressure, and triglycerides), lipid factor (cholesterol and triglycerides), and lifestyle factor (physical activity and smoking). In multivariate Cox models, the age-adjusted hazard ratio for insulin resistance factor during the 22-year follow-up was 1.28 (95% CI 1.10 to 1.50) with regard to CHD risk and 1.64 (95% CI 1.29 to 2.08) with regard to stroke risk. Lipid factor predicted the risk of CHD but not that of stroke, and lifestyle factor predicted a reduced CHD risk. Factor analysis including only 6 risk factor variables proposed to be central components of insulin resistance syndrome (body mass index, subscapular skinfold, AUC insulin, AUC glucose, mean blood pressure, and triglycerides) produced only a single insulin resistance factor that predicted the risk of CHD and stroke independently of other risk factors.

Determination of serum insulin concentration during intravenous glucose tolerance testing of healthy bulls

To determine the insulin response curve during IV glucose tolerance testing of mature Holstein bulls. 8 Holstein bulls between 5 and 8 years old and weighing between 911.5 and 1035.5 kg. A 50% glucose solution was rapidly administered IV so that each bull received a mean dose of 258 mg of glucose/kg of body weight. Serum glucose and insulin concentrations were determined before and 30, 60, 120, and 240 minutes after glucose infusion. Serum glucose concentrations 30 and 60 minutes after infusion were significantly greater than baseline concentration. Concentrations returned to baseline values 120 minutes after infusion. Serum insulin concentration was significantly greater 30 minutes after glucose administration, compared with baseline and 240-minute concentrations. Intravenous glucose tolerance testing of mature Holstein bulls resulted in a characteristic insulin response curve. Baseline and peak insulin concentrations were higher in these bulls, compared with values reported for mature Norwegian Red cows.

Glucose refractoriness of β-cells from fed fa/fa rats is ameliorated by nonesterified fatty acids

The aim of this study was to characterize the glucose responsiveness of individual beta-cells from fa/fa rats under ad libitum feeding conditions. Enlarged intact islets from fed fa/fa rats had a compressed insulin response curve to glucose compared with smaller islets. Size-sorted islets from obese rats yielded beta-cells whose glucose responsiveness was assessed by reverse hemolytic plaque assay to determine whether glucose refractoriness was caused by a decreased number of responsive cells or output per cell. In addition, the effects of palmitic acid on glucose-stimulated insulin secretion were assessed because of evidence that nonesterified fatty acids have acute beneficial effects. Two- to threefold more beta-cells from >250 microm diameter (large) islets than <125 microm diameter (small) or lean islets responded to low glucose. Increasing the glucose (8.3-16.5 mM) induced a >10-fold increase in recruitment of active cells from small islets, compared with only a 2.6-fold increase in large islets. This refractoriness was partially reversed by preincubation of the cells in low glucose for 2 h. In addition, secretion per cell of the large islet beta-cell population was significantly reduced compared with lean beta-cells, so that the overall response capacity of large but not small islet beta-cells was significantly reduced at high glucose. Therefore, continued near-normal function of the beta-cells from small islets of fa/fa rats seems crucial for glucose responsiveness. Incubation of beta-cells from large islets with palmitic acid normalized the secretory capacity to glucose mainly by increasing recruitment and secondarily by increasing secretion per cell. In conclusion, these studies demonstrate refractoriness to glucose of beta-cells from large islets of fa/fa rats under ad libitum feeding conditions. When acutely exposed to nonesterified fatty acids, islets from fa/fa rats have a potentiated insulin response despite chronic elevation of plasma lipids in vivo.

Vagotomy Suppresses Cephalic Phase Insulin Release in Sheep

The effect of selective vagotomy of the abomasum, pylorus, duodenum and liver on insulin release during the cephalic phase of digestion was investigated in wethers and lactating ewes. Electrical stimulation of the cervical vagus nerves was carried out to test the completeness of the vagotomies performed. In experiment 1, using wethers, the abomasal, pyloric and duodenal branches (ADV; n = 7) or the hepatic, abomasal, pyloric and duodenal branches (HADV; n = 10) of the ventral and/or dorsal vagus nerves were cut; a third group of wethers underwent sham-operation (SO; n = 8). In experiment 2, vagotomy (ADV; n = 5) or sham-operations (SO; n = 5) were carried out in lactating ewes. Jugular blood was drawn before and after presentation of food for glucose and insulin determination (experiments 1 and 2) or before, during and after the electrical stimulation of the peripheral ends of the cut cervical vagus nerves in randomly selected lactating ewes (experiment 3: ADV = 3, SO = 3) and wethers (experiment 4: ADV = 4, HADV = 4, SO = 4), for determination of insulin only. Presentation of food caused an immediate and significant (P < 0.05) rise in plasma insulin levels in SO animals compared with ADV or HADV wethers (experiment 1) or ADV ewes (experiment 2) without any significant change in blood glucose concentrations. In comparison with the SO group the baseline-corrected areas under the insulin response curve were significantly (P < 0.05) smaller for the respective vagotomized groups for periods 1-2, 2-4 and 4-6 min (experiment 1) and 1-2 and 2-4 min (experiment 2) after presentation of food. Total area under the response curve for 10 min was significantly (P < 0.05) lower (experiment 1) and tended (P < 0.10) to be lower (experiment 2) for the vagotomized groups compared with that of the control groups. Direct electrical stimulation of the cervical vagus nerves raised plasma insulin concentrations to significantly (P < 0.05) higher levels in the SO ewes but not in the ADV ewes (experiment 3). It was also evident that in experiment 1, HADV did not have any additive effect over that achieved by ADV alone. These results indicate that the vagal innervation of the gut mediates insulin release during the cephalic phase of feeding in sheep. It is concluded that insulin secretion from the pancreatic -cells in response to either food-related reflex activation of the vagal nuclei in the hypothalamus or direct cervical vagus nerve stimulation is mediated through the vagal efferent fibres carried in the abomasal, pyloric and duodenal branches of the vagus nerves in sheep.

Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans.

In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either saline or nicotinic acid (NA) to deplete their plasma FFA pool, followed by an intravenous bolus of glucose. NA treatment resulted in a fall in basal insulin concentrations of 35 and 45% and in the area under the insulin response curve (area under the curve [AUC]) to glucose of 47 and 42% in the 24- and 48-h fasted individuals, respectively. The 48-h fasted subjects underwent the same procedure with the addition of a coinfusion of Intralipid plus heparin (together with NA) to maintain a high concentration of plasma FFAs throughout the study. The basal level and AUC for insulin were now completely normalized (C-peptide profiles paralleled those for insulin). To assess the effect of an overnight fast, nonobese (n = 6) and obese (n = 6) subjects received an infusion of either saline or NA, followed by a hyperglycemic clamp (200 mg/dl). The insulin AUC in response to glucose was unaffected by lowering of the FFA level in nonobese subjects, but fell by 29% in the obese group. The data clearly demonstrate that in humans, the rise in circulating FFA levels after 24 and 48 h of food deprivation is critically important for pancreatic beta-cell function both basally and during subsequent glucose loading. They also suggest that the enhancement of GSIS by FFAs in obese individuals is more prominent than that seen in their nonobese counterparts.

Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.

Several studies have shown that hyperinsulinemia is associated with the risk of coronary heart disease, but information on the association of hyperinsulinemia with the risk of stroke is limited. We investigated the association of hyperinsulinemia with the risk of stroke during a 22-year follow-up of the Helsinki Policemen Study population. The study was based on a cohort of 970 men aged 34 to 64 years who were free of cerebrovascular disease, other cardiovascular disease, or diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the insulin response curve during oral glucose tolerance test was used as a composite variable reflecting plasma insulin levels. During the 22-year follow-up, 70 men had a fatal or nonfatal stroke. Hyperinsulinemia (highest area under the insulin response curve quintile compared with the combined 4 lower quintiles) was associated with the risk of stroke (age-adjusted hazard ratio, 2.12; 95% CI, 1.28 to 3.49), but not independently of other risk factors (multiple-adjusted hazard ratio, 1.54; 95% CI, 0.90 to 2.62), which was mainly due to the impact of obesity, particularly upper body obesity, with subscapular skinfold thickness used as an index. Of other risk factors, upper body obesity, blood pressure, and smoking were independent predictors of the risk of stroke. Hyperinsulinemia was associated with the risk of stroke in Helsinki policemen during the 22-year follow-up, but not independently of other risk factors, particularly upper body obesity.

Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.

The Helsinki Policemen Study is one of the first prospective epidemiological studies demonstrating an association of hyperinsulinemia to the risk of coronary heart disease (CHD). The aim of the present study was to investigate the predictive value of hyperinsulinemia with regard to CHD risk during a 22-year follow-up of the Helsinki Policemen Study population. The study was based on a cohort of 970 men who were 34 to 64 years of age and free of CHD, other cardiovascular disease, and diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test (OGTT) with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the plasma insulin response curve (AUC insulin) during OGTT was used as a composite variable reflecting plasma insulin levels. During the 22-year follow-up, 164 men had a major CHD event (CHD death or nonfatal myocardial infarction). Age-adjusted hazard ratios for a major CHD event comparing men in the highest AUC insulin quintile with those in the combined 4 lower quintiles during 5-, 10-, 15-, and 22-year follow-up periods were 3.29 (95% CI, 1.56 to 6.91), 2.72 (95% CI, 1.67 to 4.42), 2.14 (95% CI, 1.43 to 3.21), and 1.61 (95% CI, 1.14 to 2.27), respectively. Further adjustment for other risk factors attenuated these hazard ratios to 2.36 (95% CI, 1.00 to 5.57), 2.29 (95% CI, 1.31 to 4.02), 1.76 (95% CI, 1.09 to 2.82), and 1.32 (95% CI, 0.89 to 1.97), respectively. Hyperinsulinemia predicted CHD risk in Helsinki policemen over the 22-year follow-up, and to a large extent independently of other CHD risk factors, but its predictive value diminished with lengthening follow-up time.

Usefulness of revised fasting plasma glucose criterion and characteristics of the insulin response to an oral glucose load in newly diagnosed Japanese diabetic subjects.

To examine the usefulness of the revised criterion for fasting plasma glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic Association (ADA) (126 mg/dl, 7 mmol/l), and to characterize insulin response during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese diabetic subjects. A series of 2,121 Japanese subjects underwent a 75-g OGTT (0-3 h) and were divided into three groups (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus [DM] according to the current World Health Organization criteria. After the cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed, the usefulness of the ADA criterion for FPG was examined by comparing diagnostic parameters (sensitivity, specificity, and accuracy) with those for the cutoff value of 140 mg/dl. To assess insulin response, both the insulinogenic index (IsIx), a marker of early secretion, and the area under the insulin response curve (AUCins), a marker of total secretion, were compared between the DM, NGT, and IGT groups. First, the FPG cutoff value distinguishing NGT from diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31), the same specificity (1.00), and a higher accuracy (0.82 vs. 0.74) than an FPG of 140 mg/dl, and it had a higher specificity (1.00 vs. 0.86) with a slightly lower accuracy (0.82 vs. 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31) and accuracy (0.80 vs. 0.74) and a similar specificity (0.97 vs. 1.00) compared with an FPG of 140 mg/dl, and it had a higher specificity (0.97 vs. 0.82) with the same accuracy (0.80) as an FPG of 113 mg/dl. Third, the DM group showed the lowest IsIx among the three groups at all FPG values. The AUCIns in the DM group increased along with FPG, reached the maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher in the DM group than in the NGT group at FPG values > or = 100 mg/dl. The revised ADA criterion for FPG of 126 mg/dl may improve diagnostic sensitivity without loss of specificity in Japanese diabetic subjects when compared with an FPG criterion of 140 mg/dl. Although early insulin secretion was impaired, total insulin secretion did not seem to be reduced in newly diagnosed Japanese diabetic subjects.

Glucose-induced thermogenesis, inhibition of lipid oxidation rate and autonomic dysfunction in non-diabetic obese women.

The aim of this study was to look for a relationship between autonomic dysfunction and alterations in glucose- induced thermogenesis (GIT) and lipid oxidation rate in obese non-diabetic women. 37 obese women, 20 with impaired cardiac autonomic function tests (group 1) were matched with 17 women with normal tests (group 2) according to age, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass (FM) and fat free mass (FFM). A series of five standardized tests was carried out, three of which were based mainly on cardiac parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip). Energy expenditure (EE), lipid and glucose oxidation rate were determined by indirect calorimetry at fasting and after an oral glucose load (75 g). Blood glucose, insulin and catecholamines responses to glucose were examined. There was no significant difference in plasma glucose, insulin, catecholamines, metabolic rate, glucose and lipid oxidation rate at fasting and plasma glucose, insulin and catecholamine responses to glucose. GIT was slightly but not significantly lower in group 1 (24.7+/-10.4 kJ) than in group 2 (46.8+/-9.0 kJ). The cumulative glucose oxidation rate did not differ significantly in the two groups. The cumulative lipid oxidation rate was significantly lower in group 1 than in group 2 (-49.4+/-4.1 vs -30.8+/-8.0, respectively, P = 0.033). It correlated negatively with the area under the curve of insulin response (r=-0.37, P=0.04). In the multivariate analysis, both autonomic dysfunction and the area under the curve of insulin response correlated significantly with the cumulative lipid oxidation rate. This study suggests that 1) the glucose-induced inhibition of the lipid oxidation rate in obese women is greater in the patients with autonomic dysfunction; 2) a decrease in sympathetic activity is likely to be involved in this phenomenon.