Insulin Resistance In Non-diabetic Women Research Articles

Silymarin Reduced Insulin Resistance in Non-Diabetic Women with Obesity.

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values (p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study.

Insulin resistance metabolomic profile in non-diabetic women with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have a higher prevalence of insulin resistance (IR) and metabolic syndrome (MetS) than controls. To evaluate IR in non-diabetic women with SLE by means of biomarkers using high-throughput metabolomic techniques. Cross-sectional study in patients with SLE. A metabolomic approach was employed using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry. MetS was evaluated according to NCEP-ATP III criteria. Seventy patients with SLE were included, out of whom 45 (64.2%) and 27 (38.5%) had IR and MetS, respectively. Patients with IR had a higher body mass index and hypertension more often than those without IR. Chronic damage and disease activity were not related to IR. A Quantose-IR score ≥ 63 was more common in patients with MetS (81.5 vs. 53.5%; p = 0.02). Quantose-IR score was also correlated with the number of criteria for MetS (r: 0.35; p = 0.003). In non-diabetic women with SLE, the prevalence of IR based on Quantose-IR score was 64.2%.

Elevated serum levels of galectin-3 binding protein are associated with insulin resistance in non-diabetic women after menopause

ObjectiveGalectin-3 binding protein (Gal-3BP) is one of the major fucosylated glycoprotein family members and has recently been implicated in non-alcoholic fatty liver disease, hyperlipaemia and coronary artery disease. Here, we analysed the serum concentrations of Gal-3BP in menopausal women to evaluate the association of circulating Gal-3BP and insulin resistance in females after menopause. Materials and methodsWe evaluated serum levels of Gal-3BP in sixty-two non-diabetic women with menopausal status for at least one year. The clinical features, biochemical profiles and homeostasis model assessment of insulin resistance (HOMA-IR) indices were obtained routinely. ResultsGal-3BP levels increased in women with higher HOMA-IR indices and were positively correlated with HOMA-IR indices. The Gal-3BP level was also an independent risk factor for a high HOMA-IR index and showed the most influence on the HOMA-IR index compared to fasting plasma glucose, triglyceride, age and body mass index. The cut-off value of the serum Gal-3BP level was 2234.32 ng/ml, with areas under the ROC curve (AUCs) of 0.68 (HOMA-IR index 1.5), 0.81 (HOMA-IR index 2.0) and 0.93 (HOMA-IR index 2.5). ConclusionSerum levels of Gal-3BP are associated with impaired insulin sensitivity in non-diabetic menopausal women.

Effect of Psyllium Supplementation on Insulin Resistance and Lipid Profile in Non-diabetic Women With Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Trial

Objectives: Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women. In addition, the risk of type2 diabetes mellitus (T2DM), hyperinsulinemia, and insulin resistance is higher among women with PCOS. Psyllium can reduce the levels of fasting blood sugar (FBS), insulin resistance, and lipid profile. Thus, the present study aimed to evaluate the effect of psyllium supplementation on insulin resistance and the lipid profile in non-diabetic women with PCOS. Materials and Methods: In this randomized double-blind placebo-controlled trial, 54 eligible non-diabetic women with PCOS aged 18-45 were recruited from an endocrinology clinic and divided into 2 groups based on their body mass index (BMI) through stratified-block randomization. Participants in intervention and placebo groups received 5 g of psyllium or cellulose microcrystalline twice a day for 8 weeks. Fasting insulin, FBS, and insulin resistance indicators including HOMA1-IR, HOMA2-IR, along with quantitative insulin sensitivity check index (QUICKI) and the lipid profile were evaluated before and after the intervention. Results: In the psyllium group, the FBS, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), HOMA1-IR, and HOMA2-IR indicators decreased significantly (P&lt;0.05) after 8 weeks, but the changes were not significant in the placebo group. The mean changes in LDL-C (0.28±0.58 and 0.11±0.67 in intervention and placebo groups, respectively, P=0.036) and QUICKI (0.01±0.03 and 0.02±0.06 in intervention and placebo groups, respectively, P=0.044) were significant between the two groups from the baseline. Conclusions: Psyllium supplementation decreased FBS, fasting insulin, and the lipid profile while improving insulin resistance in non-diabetic women with PCOS.

Meat Intake and Insulin Resistance in Women without Type 2 Diabetes.

Purpose. To examine the relationship between meat intake and insulin resistance (IR) in 292 nondiabetic women. Methods. IR was evaluated using the homeostasis model assessment (HOMA). Diet was assessed via 7-day weighed food records. Servings of very lean meat (VLM) and regular meat (meat) were indexed using the ADA Exchange Lists Program. Physical activity was assessed using accelerometers and body fat was measured using the Bod Pod. Results. Meat intake was directly related to HOMA (F = 7.4; P = 0.007). Women with moderate or high meat intakes had significantly higher HOMA levels than their counterparts. Adjusting for body fat weakened the relationship (F = 1.0; P = 0.3201). Odds ratio results showed that the low meat quartile had 67% lower odds of being IR (75th percentile) compared to their counterparts (OR = 0.33; 95% CI = 0.16–0.71). These findings changed little after adjusting for all covariates simultaneously (OR = 0.34; 95% CI = 0.14–0.83). Conversely, VLM intake was not related to HOMA, with or without the covariates. Conclusion. Moderate and high meat intakes are associated with increased insulin resistance in nondiabetic women. However, differences in body fat contribute significantly to the relationship. VLM is not predictive of IR. Prudence in the amount and type of meat consumed may be helpful in decreasing the likelihood of IR.

Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus.

The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. Women with SLE tended to have lower 25(OH)D levels (p = 0.078) and a higher frequency of 25(OH)D deficiency (defined as < 10 ng/ml) than controls (p = 0.058). Patients from the lowest quartile of the 25(OH)D range had higher PWV (p = 0.043), fasting glucose (p = 0.035), insulinemia (p ≤ 0.001), HOMA-IR (p = 0.006), C4 (p = 0.012), as well as more frequent IR (p = 0.002) and metabolic syndrome (p = 0.052) than those in the upper quartile, and no differences were found in age, body mass index (BMI), blood pressure, lipid levels and renal function. In women with SLE, 25(OH)D inversely correlated with insulin (p = 0.006), HOMA-IR (p = 0.008) and C4 (p = 0.048) and tended to correlate with fibrinogen (p = 0.060) after adjustment for BMI, age, SLEDAI, prednisone dose, renal function, inflammation markers and seasonal variation, but not with PWV. In controls, 25(OH)D correlated only with homocysteine after the same adjustment, and the correlation with PWV tended to be significant after adjustment for BMI and age (r = -0.190, p = 0.10). Low 25(OH)D levels were found to be associated with increased IR in nondiabetic women with SLE independently of BMI. Low 25(OH)D levels, but not IR, could be associated with increased arterial stiffness in these patients.

Vitamin D and Insulin Resistance in Non-Diabetic Women's Interagency HIV Study Participants

We explored the relationship between vitamin D levels and insulin resistance (IR) among 1082 nondiabetic (754 HIV-infected) women enrolled in the Women's Interagency HIV study (WIHS), a large and well-established cohort of HIV infected and uninfected women in the US. Vitamin D levels 20-29 ng/mL were considered insufficient and <20 ng/mL deficient. IR was estimated using the homeostasis model assessment (HOMA) and a clinically significant cut-off ≥2.6 was used for HOMA-IR. In the unadjusted analysis, women who were vitamin D insufficient or deficient were 1.62 (95% CI: 1.01-2.61, p=0.05) and 1.70 (95% CI: 1.11-2.60, p=0.02) times more likely to have HOMA values≥2.6 compared to women with sufficient vitamin D. The association did not remain significant after adjustment for factors associated with IR. Among the 754 HIV-infected women, current PI use (OR 1.61, 95% CI: 1.13-2.28, p=0.008) remained independently associated with HOMA ≥2.6 while vitamin D insufficiency (OR 1.80, 95% CI: 0.99-3.27, p=0.05) was marginally associated with HOMA ≥2.6 after adjustment. Ethnicity, body mass index, smoking status, and hepatitis C status were independently associated with insulin resistance in HIV-infected and uninfected women. We found a marginally significant association between vitamin D insufficiency and insulin resistance among nondiabetic HIV-infected WIHS women.

Fasting substrate oxidation in relation to habitual dietary fat intake and insulin resistance in non-diabetic women: a case for metabolic flexibility?

BackgroundMetabolic flexibility described as “the capacity of the body to match fuel oxidation to fuel availability” has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM).MethodsWe measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95).ResultsThe Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p < 0.05) and lower PA levels than Insulin Sensitive (IS) group (P < 0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2 = 0.50, p < 0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p < 0.01), independent of body fat % or distribution.ConclusionIn these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.

Relationship between Adipose Tissue Lipolytic Activity and Skeletal Muscle Insulin Resistance in Nondiabetic Women

Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity. The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects. We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods. Basal (r(s) = -0.379, P < 0.001) and insulin-suppressed (r(s) = -0.631, P < 0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P < 0.001). These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.

Insulin-Lowering Effects of Metformin in Women with Early Breast Cancer

Background Obesity has been associated with poor breast cancer outcomes. Insulin may mediate this effect, interacting with insulin receptors on breast cancer cells. Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states. If metformin lowers insulin levels in women with breast cancer, it may also improve breast cancer outcomes. Patients and Methods We administered metformin (1500 mg per day) to 32 women with early breast cancer whose baseline insulin levels were at least 45 pmol/L to determine its effect on insulin levels. Results Twenty-two (69%) women completed the 6-month intervention. Four women (12.5%) dropped out because of gastrointestinal side effects; the others withdrew for reasons not related to toxicity. Completers were similar to noncompleters for all baseline characteristics apart from global health, overall physical condition, overall quality of life, physical function, and social function (HRQOL), which was decreased in noncompleters. Metformin significantly lowered fasting insulin levels by 15.8 pmol/L (22.4%; P = .024) and improved insulin sensitivity by 25.6% ( P = .018), total cholesterol by 5.3%, and low-density lipoprotein (LDL) cholesterol by 9.1%. Metformin reduced weight by 1.9 kg (2.5%; P = .01), and it had no significant effects on HRQOL or specific gastrointestinal symptoms (appetite, nausea/vomiting, diarrhea, constipation). Conclusion Metformin significantly lowers insulin levels, and it improves insulin resistance in nondiabetic women with breast cancer. A phase III randomized trial to evaluate its effects on breast cancer outcomes is recommended.

GIP receptor mRNA expression in different fat tissue depots in postmenopausal non-diabetic women

Aims Gastric inhibitory polypeptide (GIP) is an insulinotropic duodenal hormone released in response to meals. Recent studies in rodents suggested that GIP directly links overnutrition to obesity. Despite evidence for GIP effects on fat metabolism in humans, the GIP receptor (GIPR) has not been identified in fat tissues. We identified the GIPR gene in human subcutaneous and visceral fat tissues and tested the hypothesis that that the expression of this gene is influenced by central obesity and weight loss. Methods GIPR gene mRNA expression in subcutaneous fat tissue biopsies ( n = 70) and in paired subcutaneous and visceral fat tissue samples ( n = 25) of non-diabetic postmenopausal women was studied by real-time reverse transcription polymerase chain reaction. The effect of weight reduction on GIPR gene expression in subcutaneous fat tissue was studied in a subset of 14 women. Results GIPR adipose tissue gene expression was significantly lower in insulin resistant obese non-diabetic women ( p = 0.004). The GIPR mRNA expression was higher in the visceral fat tissue compared with subcutaneous fat ( p < 0.001). Despite adjustment for obesity-associated variables, waist circumference was the most significant predictor of GIPR gene expression in subcutaneous fat depot ( F = 4.066; β = − 0.997; p = 0.0001) and, together with fasting insulin levels, in visceral fat ( F = 3.553; β = − 0.507 and β = 0.495; p = 0.0001). Moderate weight reduction did not change gene expression levels of the GIPR gene ( p = 0.085). Conclusions Decreased expression of the GIPR gene in subcutaneous fat tissue is associated with signs of insulin resistance in non-diabetic women with central obesity and demonstrates that fasting hyperinsulinemia is a possible negative regulator of GIPR gene expression in subcutaneous fat. Higher GIPR gene expression levels in visceral fat vs. subcutaneous fat reflect regional differences in adipose tissue biology. Moderate weight reduction did not change gene expression levels of GIPR in subcutaneous fat.

Glucose tolerance and insulin resistance after danazol treatment

SummarySummaryBlood glucose and serum insulin concentrations were measured during an oral glucose tolerance test in nine non-diabetic women before and 6 weeks alter starting treatment with danazol for pelvic endometriosis.Danazol induced a mild deterioration in glucose tolerance and a marked increase in the insulin response to glucose loading. Sex hormone binding globulin concentrations were reduced by 80 per cent but there was no change in total testosterone and oestradiol concentrations.These data confirm that danazol increases insulin resistance in non-diabetic women, probably as a result of its androgenic properties. Danazol treatment should probably be avoided in women with impaired glucose tolerance.