Insulin resistance and obesity in childhood
(Chiarelli and Marcovecchio 2008) Download
Childhood obesity is a significant health problem that has reached epidemic proportions around the world and is associated with several metabolic and cardiovascular complications. Insulin resistance is a common feature of childhood obesity and is considered to be an important link between adiposity and the associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance is also a key component of the metabolic syndrome, and its prevalence in the paediatric population is increasing, particularly among obese children and adolescents. Several factors are implicated in the pathogenesis of obesity-related insulin resistance, such as increased free fatty acids and many hormones and cytokines released by adipose tissue. Valid and reliable methods are essential to assess the presence and the extent of insulin resistance, the associated risk factors and the effect of pharmacological and lifestyle interventions. The two most common tests to assess insulin resistance are the hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose tolerance test utilizing the minimal model. However, both these tests are not easily accomplished, are time consuming, expensive and invasive. Simpler methods to assess insulin resistance based on surrogate markers derived from an oral glucose tolerance test or from fasting insulin and glucose levels have been validated in children and adolescents and widely used. Given the strong association between obesity, insulin resistance and the development of metabolic syndrome and cardiovascular disease, prevention and treatment of childhood obesity appear to be essential to prevent the development of insulin resistance and the associated complications.
The relationship of vitamin B12 to carbohydrate metabolism and diabetes mellitus
(Chow and Stone 1957) Download
Decline in physical fitness from childhood to adulthood associated with increased obesity and insulin resistance in adults
(Dwyer, Magnussen et al. 2009) Download
OBJECTIVE: To examine how fitness in both childhood and adulthood is associated with adult obesity and insulin resistance. RESEARCH DESIGN AND METHODS: A prospective cohort study set in Australia in 2004-2006 followed up a cohort of 647 adults who had participated in the Australian Schools Health and Fitness Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness assessment during the survey. Outcome measures were insulin resistance and obesity, defined as a homeostasis model assessment index above the 75th sex-specific percentile and BMI >or=30 kg/m(2), respectively. RESULTS: Lower levels of child cardiorespiratory fitness were associated with increased odds of adult obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6-5.6]) and insulin resistance (1.7 [1.1-2.6]). A decline in fitness level between childhood and adulthood was associated with increased obesity (4.5 [2.6-7.7]) and insulin resistance (2.1 [1.5-2.9]) per unit decline. CONCLUSIONS: A decline in fitness from childhood to adulthood, and by inference a decline in physical activity, is associated with obesity and insulin resistance in adulthood. Programs aimed at maintaining high childhood physical activity levels into adulthood may have potential for reducing the burden of obesity and type 2 diabetes in adults.
Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology
(Godsland and Johnston 2008) Download
Clustering of risk factors for coronary heart disease and diabetes is well established, particularly in relation to insulin resistance. To determine whether evaluation of risk factor clustering will contribute to risk assessment, it is first necessary to discriminate co-association between risk factors from correlation. We undertook this in a large homogenous group, using a sophisticated measure of insulin sensitivity and a broad range of risk factors. Cross-sectional analysis of an occupational cohort using regression and factor analyses was performed. Subjects were 472 apparently healthy white men. The main outcome measures were insulin sensitivity, S(I), by minimal model analysis of the intravenous glucose tolerance test plus liver function and hematologic variables, including the inflammation indices, leukocyte count, and erythrocyte sedimentation rate. The S(I) correlated independently with serum gamma-glutamyl transferase (GGT), aspartate transaminase, and alkaline phosphatase activities; blood pressure; leukocyte count; and erythrocyte sedimentation rate (P < .01). On factor analysis, the factor that explained the greatest proportion of the variance (56.7%) included, in decreasing order of factor loading, triglycerides, S(I) (negative), body mass index, high-density lipoprotein cholesterol (negative), insulin, uric acid, and GGT activity (loadings >0.40). Mean arterial pressure was not a feature (loading 0.29), neither were indices of subclinical inflammation. In apparently healthy men, blood pressure and indices of subclinical inflammation do not cluster with other insulin resistance-related risk factors, despite correlating with insulin sensitivity. In contrast, both GGT activity and uric acid concentrations correlated with insulin sensitivity and co-associated with insulin resistance-related risk factors and are therefore components of a true risk factor cluster.
Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats
(Jain, Croad et al. 2010) Download
Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 mug Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats.
Glycemic index: overview of implications in health and disease
(Jenkins, Kendall et al. 2002) Download
The glycemic index concept is an extension of the fiber hypothesis, suggesting that fiber consumption reduces the rate of nutrient influx from the gut. The glycemic index has particular relevance to those chronic Western diseases associated with central obesity and insulin resistance. Early studies showed that starchy carbohydrate foods have very different effects on postprandial blood glucose and insulin responses in healthy and diabetic subjects, depending on the rate of digestion. A range of factors associated with food consumption was later shown to alter the rate of glucose absorption and subsequent glycemia and insulinemia. At this stage, systematic documentation of the differences that exist among carbohydrate foods was considered essential. The resulting glycemic index classification of foods provided a numeric physiologic classification of relevant carbohydrate foods in the prevention and treatment of diseases such as diabetes. Since then, low-glycemic-index diets have been shown to lower urinary C-peptide excretion in healthy subjects, improve glycemic control in diabetic subjects, and reduce serum lipids in hyperlipidemic subjects. Furthermore, consumption of low-glycemicindex diets has been associated with higher HDL-cholesterol concentrations and, in large cohort studies, with decreased risk of developing diabetes and cardiovascular disease. Case-control studies have also shown positive associations between dietary glycemic index and the risk of colon and breast cancers. Despite inconsistencies in the data, sufficient, positive findings have emerged to suggest that the dietary glycemic index is of potential importance in the treatment and prevention of chronic diseases.
Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome
(Hahn, Haselhorst et al. 2006) Download
Insulin resistance (IR) and central obesity are common features of the polycystic ovary syndrome (PCOS). Vitamin D is thought to play a role in the pathogenesis of type 2 diabetes by affecting insulin metabolism. The aim of our study was to investigate the effect of 25-hydroxyvitamin D (25-OH-VD) on metabolic parameters and IR in PCOS. In 120 untreated PCOS patients (median age 28 years) levels of 25-OH-VD (radioimmunoassay method provided by DiaSorin), calcium and anorganic phosphate were measured. In addition, endocrine and metabolic variables were evaluated and a glucose tolerance test was performed to assess indices of IR. In the entire PCOS cohort, 25-OH-VD concentrations were negatively correlated with body mass index (r=-0.2765), body fat (r=-0.2490), HOMA-IR (r=-0.1947), hyperinsulinemia (r=-0.1892) and leptin levels (r=-0.2834), and positively correlated with HDL cholesterol (r=0.2630) (all p<0.05). Subgroup analysis of lean, overweight and obese women revealed significant higher 25-OH-VD levels in lean women. Differences remained significant when women were divided according to their 25-OH-VD levels. Women with hypovitaminosis D (<9 ng/ml) had higher mean BMI, indices of IR and leptin levels compared to women with normal serum levels (all p<0.05). Analysis of vitamin D and biochemical endocrine PCOS features revealed a significant correlation only between 25-OH-VD and sex hormone-binding globulin as well as the free androgen index. In conclusion, in PCOS women, low 25-OH-VD levels are associated with obesity and insulin resistance but not with PCOS per se.
Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans
(Katz, Nambi et al. 2000) Download
Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
Insulin resistance: lifestyle and nutritional interventions
(Kelly 2000) Download
Insulin resistance appears to be a common feature and a possible contributing factor to several frequent health problems, including type 2 diabetes mellitus, polycystic ovary disease, dyslipidemia, hypertension, cardiovascular disease, sleep apnea, certain hormone-sensitive cancers, and obesity. Modifiable factors thought to contribute to insulin resistance include diet, exercise, smoking, and stress. Lifestyle intervention to address these factors appears to be a critical component of any therapeutic approach. The role of nutritional and botanical substances in the management of insulin resistance requires further elaboration; however, available information suggests some substances are capable of positively influencing insulin resistance. Minerals such as magnesium, calcium, potassium, zinc, chromium, and vanadium appear to have associations with insulin resistance or its management. Amino acids, including L-carnitine, taurine, and L-arginine, might also play a role in the reversal of insulin resistance. Other nutrients, including glutathione, coenzyme Q10, and lipoic acid, also appear to have therapeutic potential. Research on herbal medicines for the treatment of insulin resistance is limited; however, silymarin produced positive results in diabetic patients with alcoholic cirrhosis, and Inula racemosa potentiated insulin sensitivity in an animal model.
Associations of visceral adiposity and exercise participation with C-reactive protein, insulin resistance, and endothelial dysfunction in Korean healthy adults
(Kim, Valentine et al. 2008) Download
The aim of the current study was to examine the associations of visceral adiposity and exercise participation with C-reactive protein (CRP), insulin resistance, and endothelial dysfunction in Korean adults selected from the general population. We studied 160 Korean adults (aged 41.3 +/- 13.0 years; n = 38 men and n = 122 women) who volunteered in a health promotion program. Subjects were divided into 2 groups based upon spontaneous exercise participation for using a cross-sectional approach. We measured anthropometric factors (body mass index [BMI], percentage body fat, waist-hip ratio [WHR], and abdominal fat area by computed tomographic scanning), blood pressure (BP), blood levels of glucose, lipids, fibrinogen, CRP, leptin, hemoglobin A(1c), homeostasis model assessment (HOMA), and carotid intima media thickness (IMT; via ultrasonography). Associations among the variables were assessed by Pearson partial correlation and linear regression, controlling for age and sex. Independent t tests were used to assess differences between exercise participants and nonparticipants. Significance was accepted at P < .05. As expected, the measures of adiposity (BMI, percentage body fat, WHR, abdominal fat area) were highly correlated with each other (r = .49-.86, P < .01). Blood levels of high-sensitivity CRP (hsCRP), leptin, and HOMA were modestly correlated with all measures of adiposity. Visceral fat area was the most important predictor of hsCRP, explaining 19.6% of the variance using stepwise linear regression analysis (P < .01). As visceral fat area tertiles increased from low to high, a significant stepwise increment in blood levels of CRP (P < .001), HOMA (P = .005), and left carotid IMT (P = .035) was observed. However, hsCRP and HOMA were not significantly different when compared across whole-body fat tertiles. Systolic BP, diastolic BP, and left carotid IMT were modestly correlated with WHR and visceral fat area (P < .05); but systolic BP and diastolic BP were also correlated with BMI and percentage body fat (P < .05). Therefore, the relative importance of central adiposity as opposed to total body fatness in endothelial dysfunction is unclear. Compared with the nonexercise group, exercise participants had significantly lower (P < .05) WHR, visceral fat area, ratio of visceral fat area to subcutaneous area, hsCRP, hemoglobin A(1c), and HOMA, with no significant differences in BMI, percentage body fat, and physical fitness. Central obesity with high visceral fat is strongly associated with blood level of hsCRP, insulin resistance, and endothelial dysfunction-related factors in healthy Korean adults. In addition, exercise participation, even in the absence of difference in physical fitness, may be protective against development of central obesity and insulin resistance in this understudied Korean population.
Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship with Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting
(Knoblovits, Costanzo et al. 2009) Download
Erectile dysfunction (ED) is associated with metabolic and endocrine diseases including obesity, metabolic syndrome (MS) and Type 2 Diabetes Mellitus (DM2). Insulin-resistance (IR), present in patients with obesity, MS and DM2, causes disturbances in the signaling pathways required for nitric oxide production with subsequent endothelial dysfunction. In addition, IR also appears to alter testosterone production. We evaluated in eugonadal ED patients: 1) the presence of obesity and IR; 2) testosterone levels and their association with obesity and IR and 3) the degree of ED according to the presence of IR. In a prospective study 78 eugonadal patients with ED (group P) where recruited and compared with 17 men without ED as a control group (group C). The erectile function was evaluated according the International Index of Erectile Function 5 (IIEF-5). IR was measured by HOMA. IR was defined as a HOMA >/= 3. Results: patients with ED had a significant higher BMI, waist circumference (WC), HOMA values an prevalence of IR when compared to group C. Total (TT) and bioavailable testosterone (BT) levels were lower in group P compared to group C. There was a significantly negative correlation between HOMA and IIEF-5, HOMA and TT, WC and IIEF-5, WC and TT and between WC and BT. Group P patients with IR had a higher WC and lower IIEF-5 score when compared with patients in group P without IR. In conclusion: Patients with ED show a higher BMI, WC, and HOMA and lower levels of TT and BT. There is a negative correlation between erectile function and IR and abdominal obesity. The TT levels are lower in patients with increased BMI, WC and IR. However, a negative correlation was shown only between BT (biologically active fraction) and abdominal obesity.
Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects
(Muniyappa, Karne et al. 2006) Download
Glucosamine is a popular nutritional supplement used to treat osteoarthritis. Intravenous administration of glucosamine causes insulin resistance and endothelial dysfunction. However, rigorous clinical studies evaluating the safety of oral glucosamine with respect to metabolic and cardiovascular pathophysiology are lacking. Therefore, we conducted a randomized, placebo-controlled, double-blind, crossover trial of oral glucosamine at standard doses (500 mg p.o. t.i.d.) in lean (n = 20) and obese (n = 20) subjects. Glucosamine or placebo treatment for 6 weeks was followed by a 1-week washout and crossover to the other arm. At baseline, and after each treatment period, insulin sensitivity was assessed by hyperinsulinemic-isoglycemic glucose clamp (SI(Clamp)) and endothelial function evaluated by brachial artery blood flow (BAF; Doppler ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound with microbubble contrast) before and during steady-state hyperinsulinemia. Plasma glucosamine pharmacokinetics after oral dosing were determined in each subject using a high-performance liquid chromatography method. As expected, at baseline, obese subjects had insulin resistance and endothelial dysfunction when compared with lean subjects (SI(Clamp) [median (Muniyappa, Karne et al.)] = 4.3 [2.9-5.3] vs. 7.3 [5.7-11.3], P < 0.0001; insulin-stimulated changes in BAF [% over basal] = 12 [-6 to 84] vs. 39 [2-108], P < 0.04). When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was approximately 150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects.
The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: a randomised controlled trial
(Petchey, Hickman et al. 2009) Download
BACKGROUND: Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. METHODS/DESIGN: This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. DISCUSSION: To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.
Insulin resistance and obesity
(Schwartz and Kahn 1999) Download
Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose
(Yokoyama, Emoto et al. 2004) Download
The purpose of the study was to investigate whether quantitative insulin sensitivity check index (QUICKI) and the reciprocal index of homeostasis model assessment (1/HOMA-IR) are excellent surrogate indexes of insulin resistance in type 2 diabetic patients with various ranges of fasting plasma glucose. One hundred eight type 2 diabetic patients were divided into tertiles according to fasting levels of plasma glucose (FPG) [T1: 4.2 < or = FPG (mmol/liter) < 6.5, n = 36; T2: 6.5 < or = FPG < 8.1, n = 36; T3: 8.1 < or = FPG < or = 11.1, n = 36]. The association between QUICKI or 1/HOMA-IR and insulin resistance index assessed by euglycemic hyperinsulinemic clamp (Clamp-IR) was investigated in each group. QUICKI was strongly correlated with Clamp-IR in all groups (r = 0.615 in T1, r = 0.659 in T2, and r = 0.788 in T3; all subjects, r = 0.691; all P < 0.001). Reciprocal of HOMA-IR also highly correlated with Clamp-IR in all groups (r = 0.600, r = 0.721, and r = 0.730, respectively; all subjects, r = 0.685; all P < 0.001). In conclusion, QUICKI and the reciprocal index of HOMA were highly correlated with Clamp-IR in type 2 diabetic patients with relatively wide ranges of fasting plasma glucose.
Chiarelli, F. and M. L. Marcovecchio (2008). "Insulin resistance and obesity in childhood." Eur J Endocrinol 159 Suppl 1: S67-74.
Chow, B. F. and H. H. Stone (1957). "The relationship of vitamin B12 to carbohydrate metabolism and diabetes mellitus." Am J Clin Nutr 5(4): 431-9.
Dwyer, T., C. G. Magnussen, et al. (2009). "Decline in physical fitness from childhood to adulthood associated with increased obesity and insulin resistance in adults." Diabetes Care 32(4): 683-7.
Godsland, I. F. and D. G. Johnston (2008). "Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology." Metabolism 57(9): 1190-7.
Hahn, S., U. Haselhorst, et al. (2006). "Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome." Exp Clin Endocrinol Diabetes 114(10): 577-83.
Jain, S. K., J. L. Croad, et al. (2010). "Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats." Mol Nutr Food Res.
Jenkins, D. J., C. W. Kendall, et al. (2002). "Glycemic index: overview of implications in health and disease." Am J Clin Nutr 76(1): 266S-73S.
Katz, A., S. S. Nambi, et al. (2000). "Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans." J Clin Endocrinol Metab 85(7): 2402-10.
Kelly, G. S. (2000). "Insulin resistance: lifestyle and nutritional interventions." Altern Med Rev 5(2): 109-32.
Kim, K., R. J. Valentine, et al. (2008). "Associations of visceral adiposity and exercise participation with C-reactive protein, insulin resistance, and endothelial dysfunction in Korean healthy adults." Metabolism 57(9): 1181-9.
Knoblovits, P., P. R. Costanzo, et al. (2009). "Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship with Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting." J Androl.
Muniyappa, R., R. J. Karne, et al. (2006). "Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects." Diabetes 55(11): 3142-50.
Petchey, W. G., I. J. Hickman, et al. (2009). "The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: a randomised controlled trial." BMC Nephrol 10: 41.
Schwartz, M. W. and S. E. Kahn (1999). "Insulin resistance and obesity." Nature 402(6764): 860-1.
Yokoyama, H., M. Emoto, et al. (2004). "Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose." J Clin Endocrinol Metab 89(3): 1481-4.