Mean Fasting Insulin Concentrations Research Articles

Age- and sex-specific reference values for fasting serum insulin levels and insulin resistance/sensitivity indices in healthy Iranian adults: Tehran Lipid and Glucose Study

ObjectivesIncreased insulin concentration is a surrogate for insulin resistance and early assessment of fasting insulin may help in identifying those who are potentially at high risk of type 2 diabetes, hypertension, and cardiovascular disease. The aim of this study was to determine age- and sex-related reference values for serum insulin and insulin resistance/sensitivity indices in Iranian subjects. Design and methodsSerum insulin levels were measured by electrochemiluminescence immunoassay in 5786 participants of the Tehran Lipid and Glucose Study. After application of exclusion criteria, 309 non-obese healthy subjects (124 men and 185 women), aged 24–83y, were included. The International Federation of Clinical Chemistry guidelines (non-parametric method) and the robust method were used for determining reference values. ResultsOverall 95% reference values for fasting insulin were 1.61–11.37, 2.34–11.98, and 2.11–12.49μU/mL in men, women, and total population respectively. Mean fasting insulin concentration showed a decreasing trend with age in both genders (p for trend ≤0.001). Age, waist circumference, and systolic blood pressures were biological determinants of fasting insulin in both genders; in addition, insulin was modulated by triglycerides in men and fasting glucose in women. Reference intervals for HOMA1-IR, HOMA2-IR, and QUICKI were 0.63–2.68, 0.40–1.80, and 0.33–0.42, respectively. ConclusionThis study presents the first set of reference values for fasting serum insulin to be 2–12μU/mL for both genders in a healthy sample of Iranian adults along with the reference values for insulin resistance/sensitivity indices. These values could be used for identifying subjects with insulin resistance in epidemiological and clinical research.

Impact of activated vitamin D on insulin resistance in nondiabetic chronic kidney disease patients

Although vitamin D deficiency has been associated with increased insulin resistance, a causal link has not been established. Interpreting the relationship has been confounded by a close correlation between vitamin D deficiency and obesity. The current clinical approach of assessing endogenous 25-hydroxyvitamin D (25(OH)D) concentrations in patients with chronic kidney disease (CKD), and independently administering activated vitamin D (AD), allows a unique opportunity to clarify cause and effect in the relationship of vitamin D, obesity and insulin resistance. We assessed how 25(OH)D and body mass index (BMI) related to fasting insulin concentrations in 120 nondiabetic patients with CKD. In addition, we described how treatment with AD modified these relationships. In the full cohort, fasting insulin concentrations varied inversely with both 25(OH)D (r = -0·22, P = 0·02) and BMI (r = -0·36, P < 0·0001). The administration of AD altered these relationships. In individuals treated with AD, there was no association between 25(OH)D and fasting insulin, and the mean fasting insulin concentrations were significantly lower than in those not receiving AD (40·5 ± 22·0 vs 54·1 ± 30·9 pm, P = 0·01). In a multivariate analysis, both AD treatment and BMI were independent predictors of fasting insulin. Furthermore, obese patients treated with AD had insulin concentrations similar to nonobese patients (46·1 ± 24·9 vs 40·2 ± 21·5 pm), whereas untreated obese patients had markedly higher fasting insulin concentrations (74·4 ± 33·4 pm, P = 0·003). 25(OH)D deficiency is associated with insulin resistance in CKD. Replacement with pharmacologic doses of AD is associated with lower fasting insulin concentrations, especially in obese patients.

Acute testosterone deprivation reduces insulin sensitivity in men

In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement. Placebo-controlled, randomized trial. Twenty-two healthy male volunteers, 18-55 years old. Following screening, subjects received the gonadotrophin-releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10 g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi-weekly. With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (P = 0·02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity was also apparent in the insulin sensitivity indices homeostasis model of insulin resistance (P = 0·03) and quantitative insulin sensitivity check index (P = 0·04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed. Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.

Effects of extended regimens of the contraceptive vaginal ring on carbohydrate metabolism

BackgroundThere are few publications on the metabolic effects of extended regimens of the contraceptive vaginal ring. The aim of this study was to assess changes in fasting plasma glucose levels and insulin concentration of women using the contraceptive vaginal ring continuously over a 1-year period. Study DesignThis prospective cohort enrolled 75 women (ages 18–37 years) who used a contraceptive vaginal ring releasing 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily continuously for 84 days, followed by a 7-day ring-free interval, during 1 year. Fasting glucose and insulin levels were measured, and homeostatic model assessment was calculated at baseline and every 3 months during the 1-year study period. The repeated-measures analysis of variance test was used to analyze differences in the results of these exams over time. ResultsNone of the 75 participants had results outside the normal range in any of the assessments. There were no pregnancies during the 1-year period, and a total of 62 participants completed the study. There were no significant changes in mean fasting glucose levels (79.3 and 78.9 mg/dL at baseline and after 12 months, respectively), mean fasting insulin concentration (9.6 and 10.1 μU/mL) or mean homeostatic model assessment results (1.88% and 1.97%). ConclusionFasting plasma glucose concentration, insulin levels and homeostatic model assessment values of women using the vaginal ring on an extended regimen did not change significantly over a 1-year period.

Cross-sectional association of dietary patterns with insulin-resistant phenotypes among adults without diabetes in the Framingham Offspring Study.

Cluster analysis is a valuable tool for exploring the health consequences of consuming different dietary patterns. We used this approach to examine the cross-sectional relationship between dietary patterns and insulin-resistant phenotypes, including waist circumference, BMI, fasting insulin, 2 h post-challenge insulin, insulin sensitivity index (ISI0,120), HDL-cholesterol, TAG and blood pressure, using data from the fifth examination cycle of the Framingham Offspring Study. Among 2875 participants without diabetes, we identified four dietary patterns based on the predominant sources of energy: 'Fruits, Reduced Fat Dairy and Whole Grains', 'Refined Grains and Sweets', 'Beer' and 'Soda'. After adjusting for multiple comparisons and potential confounders, compared with the 'Fruits, Reduced Fat Dairy and Whole Grains' pattern, the 'Refined Grains and Sweets' pattern had significantly higher mean waist circumference (92.4 v. 90.5 cm; P = 0.008) and BMI (27.3 v. 26.6 kg/m2; P = 0.02); the 'Soda' pattern had significantly higher mean fasting insulin concentration (31.3 v. 28.0 microU/ml; P < or = 0.001); the 'Beer' pattern had significantly higher mean HDL-cholesterol concentration (1.46 v. 1.31 mmol/l; P < 0.001). No associations were observed between dietary patterns and ISI0,120, TAG, and systolic or diastolic blood pressure. Our findings suggest that consumption of a diet rich in fruits, vegetables, whole grains and reduced-fat dairy protects against insulin-resistant phenotypes and displacing these healthy choices with refined grains, high-fat dairy, sweet baked foods, candy and sugar-sweetened soda may promote insulin-resistant phenotypes.

Metformin monotherapy in lean women with polycystic ovary syndrome

This study was carried out to compare ovulation and pregnancy rates in response to metformin therapy in lean and obese women with polycystic ovary syndrome (PCOS). A total of 34 (17 lean and 17 obese) women with PCOS were treated with 500 mg metformin 3 times daily for 12 weeks. In the lean and obese groups, the mean body mass index was 24 and 36, and the mean fasting insulin concentrations were 12 and 21 mIU/l respectively. There was no difference between the two groups as regarding age, DHEA-S, androstenedione, 17-OH progesterone and LH concentrations. In the lean and obese groups 15/17 women (88%) and 5/17 women (29%) ovulated while 11/17 women (65%) and 3/17 women (18%) conceived respectively. Comparison between the groups was found to be statistically significant. Metformin monotherapy is very effective in improving ovulation and pregnancy rates in lean women with PCOS as compared with obese women.

Effects of trandolapril on insulin concentrations and other metabolic variables in hypertensive patients

The effects of the angiotensin-converting enzyme inhibitor trandolapril on blood pressure, insulin sensitivity, and other metabolic variables were assessed in this open study of 45 patients (27 women and 18 men; mean age, 53.1 ± 14.0 years; mean body weight, 83.4 ± 12.4 kg) with hypertension (blood pressure >140/90 mm Hg). Fasting and postprandial serum insulin and plasma glucose concentrations were measured daily before and after trandolapril administration (2 to 4 mg/d) for 12 weeks. Systolic and diastolic blood pressures and low-density lipoprotein cholesterol concentration were reduced significantly. Mean fasting insulin concentrations fell from 56.4 ± 38.0 pmol/L to 42.4 ± 28.0 pmol/L, and during an oral glucose tolerance test (OGTT) from 341.6 ± 305.0 pmol/L to 242.7 ± 229.0 pmol/L at 2 hours. The ratio of mean fasting insulin to glucose fell from 0.7 ± 0.4 to 0.5 ± 0.4, and during OGTT the ratio fell from 3.3 ± 2.0 to 2.6 ± 1.7 between 1 and 2 hours. Total cholesterol decreased and high-density lipoprotein cholesterol increased, although neither change was significant. After trandolapril treatment, insulin and glucose concentrations improved. The lack of negative effects of trandolapril on metabolic variables may offer advantages not seen with other anti-hypertensive agents such as beta-blockers and diuretics.

Race and ethnicity determine serum insulin and C-peptide concentrations and hepatic insulin extraction and insulin clearance: Comparative studies of three populations of West African Ancestry and White Americans

We examined the importance of ethnicity in terms of β-cell secretion and hepatic insulin extraction (HIE) and insulin clearance (IC) to peripheral insulin levels before and after stimulation in three populations of West African ancestry, namely African-Americans, Ghanaian immigrants, and native Ghanaians living in diverse environments, and white Americans. Following 10 to 12 hours of overnight fasting, each subject ingested a 75-g oral glucose load. Blood samples for determination of serum glucose, insulin, and C-peptide were obtained at baseline and after the oral glucose load at 30-minute intervals for 240 minutes. Basal HIE and IC were calculated as the molar ratios of C-peptide and insulin concentrations at basal steady state, and postprandial values as molar ratios of the incremental integrated C-peptide and insulin areas. Clinical characteristics of the patients were not significantly different among the four groups. During the fasting and postprandial state, serum glucose levels were not significantly different among the four groups. Surprisingly, the mean fasting insulin concentration was significantly greater in native Ghanaians (21.19± 0.93 μU/mL, P < .05) than in African-Americans (11.90 ± 1.02 μU/ML), Ghanaian immigrants (8.14 ± 0.96 μU/mL), and white Americans (7.03 ± 0.78 μU/mL). Following the oral glucose load, the mean serum peak and incremental integrated areas of insulin were significantly ( P < .05) greater in native Ghanaians, African-Americans, and Ghanaian immigrants compared with white Americans. In contrast, there were no significant differences in postprandial serum insulin responses among the three groups of West African ancestry, irrespective of country of origin or residence. Despite the higher insulin concentrations in blacks of West African ancestry compared with whites, the corresponding basal and postprandial serum C-peptide levels were not significantly different among the four groups. Mean basal and postprandial HIE and IC were significantly ( P < .05 to .01) reduced (25% to 52%) in the three populations of West African ancestry compared with the white Americans, but these values were not significantly different among the West African descendants. When comparing metabolic responses in obese (body mass index [BmI] > 27 kg/m 2) and non-obese (BMI < 27 kg/m 2) native Ghanaians, we found no significant differences in fasting insulin, C-peptide, and basal HIE or IC. Also, there were no significant relations between fasting and postprandial serum insulin, obesity indices, and HIE and IC in any of the groups. In summary, our study demonstrates that glucose-tolerant native Ghanaians, Ghanaian immigrants, and African-Americans of West African ancestry manifest hyperinsulinemia and a decreased HIE and IC compared with white Americans. We conclude that race and ethnicity may be the major determinants of the mechanism(s) of β-cell secretion, insulin action, and peripheral insulin levels and HIE or IC in humans. We speculate that thelower HIE and IC in blacks of West African descent appears to be a highly conserved metabolic trait irrespective of the country of residence.

The Effect of High-carbohydrate Intake on Substrate Utilization in Postmenopausal Women

LEARNING OUTCOME: To determine if changes in piasma lipoprotein concentrations that occur in response to high-carbohydrate, low-fat (HCLF) intake may be associated with or result from changes in substrate utilization.By implementing three diets which replaced energy from fat with carbohydrate, stepwise, over a 16-week period, we assessed the metabolic effects of a controlled increase in carbohydrate consumption in postmenopausal women. Substrate utilization was assessed by analysis of plasma metabolites [e.g. lactate, free glycerol (FG), and free fatty acids (FFA)] as well as respiratory quotient (RQ) measurements at baseline and three different timepoints throughout the study. Fasting insulin and glucose concentrations were measured to assess insulin sensitivity. Following the increase in carbohydrate consumption, mean fasting insulin concentration decreased nearly 24% and was accompanied by a concurrent drop in fasting glucose levels. Fasting RQ measurements, plasma FFA and FG concentrations following intervention did not significantly shift from baseline concentrations. Mean total-, low-density lipoprotein- and high-density lipoprotein-cholesterol were reduced an average of 5%, 9% and 13.5% of baseline values, respectively. Both plasma triglyceride (TG) and lactate were markedly elevated relative to baseline. Plasma lactate and TG correlated significantly at two of four timepoints, with plasma TG concentrations higher in those with higher plasma lactate levels. Our results suggest that during increased carbohydrate consumption, glucose oxidation increases, resulting in increased concentrations of plasma lactate. Thus, HCLF intake may promote lipogenesis by enhancing the levels of lipogenic precursors, such as lactate. The increase in lipogenesis induced through HCLF intake by increased lipogenic precursors causes the endogenous synthesis of FFA which in turn increases plasma TG. Additional research is warranted to more clearly define the relationship of increased production of lactate, a lipogenic substrate, to hypertriglyceridemia and increased plasma TG and cardiovascular disease risk in postmenopausal women.

Lipoprotein abnormalities in hirsute women. II. Compensatory responses of insulin resistance and dehydroepiandrosterone sulfate with obesity

OBJECTIVE: The purpose of our study was to further understand interrelationships between insulin. androgens. obesity. and apolipoprotein metabolism. STUDY DESIGN: In this University cross-sectional observational study for hypothesis generation. 53 women with hirsutism-hyperandrogenism were ternately divided according to body mass index into the following groups: 22 to 28 (n = 17).29 to 36 (n = 19).37 to 61 (n = 17). and 16 controls. Mean hormone and clinical parameters were compared by using the Student t test. analysis of variance. and Pearson correlation. RESULTS: Dehydroepiandrosterone sulfate correlated negatively with fasting insulin (r = 0.4. P < 0.05) and reached significance in those most obese. Unbound testosterone concentrations were 24.7. 38.9. and 31.9 ng/dl. respectively. Dehydroepiandrosterone sulfate concentrations were 2.8. 2.3. and 2.3 .... g/dl. respectively; their ratios were 13.4. 18.6. and 20.4. respectively. even though mean fasting insulin concentrations (reflecting insulin resistance) were 13.0. 20.4. and 42.6 ILU/ml. respectively. Although more atherogenic apolipoprotein profiles and higher fasting insulin concentrations were found with greater body weight. lipid-insulin interrelationships may reflect dehydroepiandrosterone sulfate interaction. CONCLUSIONS: We hypothesize that dehydroepiandrosterone sulfate dampens the effect of insulin resistance. which in turn is reflected in apolipoprotein profiles in women with hirsutism/hyperandrogenism. (AM J DaSTET GVNECOL 1992;167:1813-8.)

Lipoprotein abnormalities in hirsute women II. Compensatory responses of insulin resistance and dehydroepiandrosterone sulfate with obesity

OBJECTIVE: The purpose of our study was to further understand interrelationships between insulin, androgens, obesity, and apolipoprotein metabolism.STUDY DESIGN: In this University cross-sectional observational study for hypothesis generation, 53 women with hirsutism-hyperandrogenism were ternately divided according to body mass index into the following groups: 22 to 28 (n = 17), 29 to 36 (n = 19), 37 to 61 (n = 17), and 16 controls. Mean hormone and clinical parameters were compared by using the Student t test, analysis of variance, and Pearson correlation.RESULTS: Dehydroepiandrosterone sulfate correlated negatively with fasting insulin (r = 0.4, p \\lt 0.05) and reached significance in those most obese. Unbound testosterone concentrations were 24. 7, 38.9, and 31.9 ng/dl, respectively. Dehydroepiandrosterone sulfate concentrations were 2.8, 2.3, and 2.3 μg/dl, respectively; their ratios were 13.4, 18.6, and 20.4, respectively, even though mean fasting insulin concentrations (reflecting insulin resistance) were 13.0, 20.4, and 42.6 μU/ml, respectively. Although more atherogenic apolipoprotein profiles and higher fasting insulin concentrations were found with greater body weight, lipid-insulin interrelationships may reflect dehydroepiandrosterone sulfate interaction.CONCLUSIONS: We hypothesize that dehydroepiandrosterone sulfate dampens the effect of insulin resistance, which in turn is reflected in apolipoprotein profiles in women with hirsutism/hyperandrogenism. (AM J OBSTET GYNECOL 1992;167:1813-8.)

Impairment of glucose tolerance in hyperthyroid cats.

Intravenous glucose tolerance tests were performed in eight adult cats before and after a 4-week treatment with thyroxine. The untreated cats had a mean fasting blood glucose concentration of 7.7 +/- 0.3 mmol/l and a mean fasting insulin concentration of 88 +/- 31 pmol/l which were not significantly different from mean fasting glucose and insulin concentrations after 4 weeks of thyroxine administration (6.9 +/- 0.2 mmol/l and 101 +/- 28 pmol/l respectively). At 120 min after glucose injection, the glucose concentration in untreated cats returned to baseline concentrations as did the insulin concentration. However, in the hyperthyroid cats both glucose and insulin concentrations were significantly (P less than 0.001) higher (13.6 +/- 0.8 mmol/l and 245 +/- 17 pmol/l respectively) in comparison with the baseline and untreated cats. The t1/2 for glucose disappearance was significantly higher in the cats rendered hyperthyroid, and the glucose disposal rate constant (K) was significantly lower in this group. It is concluded that hyperthyroidism in cats leads to impairment of glucose tolerance possibly due to peripheral insulin resistance.

Effect of Age on Intravenous Glucose Tolerance and Insulin Secretion*

Twenty-seven normal volunteers whose ages ranged from 22 to 67 (mean, 37 years) were given intravenous glucose tolerance tests (IVGTT). Age was not correlated with the glucose disposal rate constant (KG), incremental insulin secretion (deltaI), or the "insulinogenic index (deltaI/DELATG). The volunteers were divided into three age groups: 1) mean age 25 years, 2) mean age 42 years, and 3) mean age 62 years. Groups 2 and 3 did not differ from Group 1 with respect to the mean level of fasting plasma glucose, KG, or deltaI/AG. Group 2 (but not Group 3) had a greater mean deltaI than Group 1, and Group 3 (but not Group 2) had a higher mean fasting insulin concentration than Group 1. No significant deterioration was detected in the intravenous glucose tolerance of healthy volunteers up to age 67. This may be attributable to the previously described feed-back system that calibrates the pancreatic beta-cell response according to the insulin sensitivity of the peripheral tissues.

A Comparative Study on the Metabolism of Human Insulin and Porcine Proinsulin in Man

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16–216 μunits/ml (insulin) and 4·2–42·8 ng/ml (proinsulin). 2. For insulin the MCR fell progressively from 34 ml kg−1 min−1 at a mean fasting insulin concentration of 3·8 μunits/ml to 11·4 ml kg−1 min−1 at the highest concentration achieved (280 μunits/ml); for proinsulin MCR averaged 3·7 ml kg−1 min−1 at a mean plasma concentration of 4·2 ng/ml and fell to 2·71 ml kg−1 min−1 at 10·7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml. 3. The half-disappearance time (T½) from the plasma, after the end of the infusion, averaged 4·3 min for insulin and 25·6 min for proinsulin. 4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98·9 ml/kg of proinsulin). 5. There was a direct correlation between T½ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T½ there was, for each hormone, no relationship between MCR and T½. 7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin. 8. The responses of serum growth hormone and Cortisol were shown to be directly related to the degree of hypoglycaemia induced.