Prenatal Chronic Hypoxia in Rats Leads to Insulin Resistance and Hypertension in Adult Offspring

Background To investigate the effects of chronic intrauterine hypoxia on insulin resistance, hypertension, and the correlation between them in adult offspring rats. Methods A total of 25 pregnant Sprague Dawley rats were randomly assigned into 4 prenatal chronic hypoxia (H) groups (10% ± 1% oxygen) and a control group (21% oxygen). The H groups were divided into whole (1–21 day), early (1–7 day), mid (8–14 day), and late (15–21 day) gestational hypoxia groups (H1, H2, H3, and H4, respectively) with pregnant rats being housed in a hypoxia box for 3 hours per day. Five male and 5 female offspring in each group were studied at 1 day, 3 months, and 6 months old. Blood pressure, fasting blood glucose, fasting serum insulin, and insulin resistance index were determined. Results The mean blood pressure of offspring rats in H groups was higher at 3 months, and further increased at 6 months old compared to the control group (P < 0.05). The fasting blood glucose and homeostasis model insulin resistance index (HOMA-IR) of male and female offspring in the whole pregnancy (H1) and early pregnancy (H2) hypoxia groups were significantly higher than those in the control group at 6 months (P < 0.05). Fasting blood glucose and HOMA-IR were positively correlated with mean blood pressure (P < 0.05). The renal mass index in H2 group was lower at 3 months, and further decreased at 6 months compared to controls (P < 0.05). The mRNA and protein levels of insulin receptor, insulin receptor substrate (IRS-1 and IRS-2) in the kidneys in hypoxia groups were significantly decreased at 6 months in H1 and H2 hypoxia groups when compared with controls (P < 0.05). Conclusions Chronic intrauterine hypoxia causes insulin resistance and hypertension in adult offspring rats through poor intrauterine growth environment, and insulin resistance is positively associated with hypertension.

Association between Selected Polymorphisms rs12086634, rs846910, rs4844880, rs3753519 of 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) and the Presence of Insulin Resistance in the Polish Population of People Living in Upper Silesia

Background: Many factors influence the development of insulin resistance, among other genetic factors. Cortisol is one of the factors that has a significant impact on the development of insulin resistance. The proteins that have a substantial effect on blood cortisol levels include 11β-hydroxysteroid dehydrogenase type 1. HSD11B1 is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. Gene encoding HSD11B1 is located on 1q32.2. This study was designed to assess the association between four polymorphic sides in HSD11B1 (rs12086634, rs846910, rs4844880, rs3753519) between subjects with and without insulin resistance in the Polish population of people living in Upper Silesia. Methods: The study included a total of 507 consecutive patients, 374 (73.77%) with and 133 (26.23%) without insulin resistance. Results: The results show that there were no statistically significant differences in the distribution of genotypes and alleles of the examined polymorphisms of the 11β-hydroxysteroid dehydrogenase type 1 gene between subjects with and without insulin resistance (determined using the HOMA-IR, insulin resistance index) and that rs846910 and rs1208663 polymorphisms of the 11β-hydroxysteroid dehydrogenase type 1 gene in the examined subjects have a significant effect on the magnitude of the HOMA-IR insulin resistance index. Conclusions: The study results suggested that genetic variation of rs846910 and rs1208663 polymorphism of the HSD11B1 gene is related to the susceptibility to insulin resistance. Our results provide a basis to begin basic research on the role of the HSD11B1 gene in the pathogenesis of insulin resistance.

The Ideal Insulin Resistance Index for c\Cardiovascular Risk Discrimination in type 2 Diabetes Mellitus

BackgroundThis study was aimed at determining the correlation between insulin resistance indices and atherogenic index as well as determining the ability of the indices to discriminate between low and high cardiovascular risk in diabetic individuals. The study involved 70 participants. Ethical approval was granted by the institution review board. Fasting plasma glucose, insulin and lipid profile were analyzed for each participant. Atherogenic index of plasma (AIP), homeostatic mode assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting glucose insulin ratio (FGIR), fasting insulin resistance index (FIRI), McAuley’s index and Raynauld’s index were calculated using the appropriate formulae. Pearson’s correlation and receiver operating characteristic (ROC) analysis were done.ResultsThe mean age of the participants was 53.34 ± 9.57 years. Males were 50%. The mean duration of type 2 diabetes in the participants was 6.29 ± 2.78 years. Each index had a strong and significant correlation with fasting plasma insulin (p<0.001). Using AIP as a marker of cardiovascular risk, 14.3% had intermediate/high risk. Among the indices, only McAuley’s index showed a statistically significant negative correlation with AIP (r= -0.453;p<0.001). None of the indices could reliably discriminate between low and intermediate/high cardiovascular risk.ConclusionThe studied indices could not predict cardiovascular risk despite their usefulness as insulin resistance markers. Further studies are needed to identify an ideal insulin resistance index that can also predict cardiovascular risk.

Relationship between insulin sensitivity and menstrual cycle is modified by BMI, fitness and physical activity in NHANES

Context There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results. Objective This study investigated variation in insulin sensitivity across the menstrual cycle and associations with BMI, physical activity and cardiorespiratory fitness. Design Data from 1906 premenopausal women in NHANES cycles 1999-2006 were analysed. Main outcome measures Menstrual cycle day was assessed using questionnaire responses recording days since last period. Rhythmic variation of plasma glucose, triglyceride and insulin, homeostatic model of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (ADIPO-IR) across the menstrual cycle were analysed using cosinor rhythmometry. Participants were assigned low or high categories of BMI, physical activity and cardiorespiratory fitness and category membership included in cosinor models as covariates. Results Rhythmicity was demonstrated by a significant cosine fit for glucose (p= 0.014) but not triglyceride (p= 0.369), insulin (p= 0.470), HOMA-IR (p=0.461) and ADIPO-IR (p= 0.335). When covariates were included, rhythmicity was observed when adjusting for: 1. BMI: glucose (p&lt; 0.001), triglyceride (p&lt; 0.001), insulin (p&lt; 0.001), HOMA-IR (p&lt; 0.001) and ADIPO-IR (p&lt; 0.001); 2. Physical activity: glucose (p&lt; 0.001), triglyceride (p= 0.006) and ADIPO-IR (p= 0.038); 3. Cardiorespiratory fitness: triglyceride (p= 0.041), insulin (p= 0.002), HOMA-IR (p= 0.004) and ADIPO-IR (p= 0.004). Triglyceride amplitude, but not acrophase, was greater in the high physical activity category compared to low (p=0.018). Conclusions Rhythmicity in insulin sensitivity and associated metabolites across the menstrual cycle are modified by BMI, physical activity and cardiorespiratory fitness.

Early arteriosclerosis and its risk factors in subjects with prediabetes and new-onset diabetes

Background: We aimed to investigate early arteriosclerosis and its risk factors in populations with prediabetes and new-onset diabetes. Materials and Methods: A total of 148 participants who did not have diabetes mellitus were assigned to three groups through an oral glucose tolerance test: the normal glucose tolerance group; the impaired glucose regulation, also known as prediabetes, group; and the new-onset type 2 diabetes mellitus group. The insulin resistance index was assessed using the Homeostatic Model Assessment of Insulin Resistance. An enzyme-linked immunosorbent assay was used to determine the level of fibroblast growth factor 21. An arteriosclerosis detector was used to measure the brachial-ankle pulse wave velocity and ankle-brachial index. baPWV, ABI, and FGF21 were used to assess early arteriosclerosis. Results: Significant differences in age, systolic blood pressure, fasting plasma glucose, 2-hour plasma glucose, 2-hour insulin, and HOMA-IR were found between the NGT group and the prediabetes and new-onset diabetes groups. All the above except 2hINS showed an increasing trend. FGF21 was higher in the new-onset diabetes group than in the NGT group, and baPWV was higher in the new-onset diabetes group than in the other two groups, but no significant difference was noted in ABI. Age, SBP, diastolic blood pressure, FPG, 2hPG, and FGF21 were positively correlated with baPWV. Moreover, BMI, SBP, DBP, FPG, 2hPG, and HOMA-IR were positively correlated with ABI. In addition, age, BMI, FPG, FGF21, and HOMA-IR were independent risk factors for baPWV, and SBP and HOMA-IR were independent risk factors for ABI. Conclusions: Patients with prediabetes and new-onset diabetes maybe have more significant early arteriosclerosis. The blood glucose level and insulin resistance index maybe the independent risk factors for early arteriosclerosis.

Adipocyte-Specific Fatty Acid-Binding Protein (AFABP) and Chemerin in Association with Gestational Diabetes: A Case-Control Study

Background. Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated. Method. The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24–28 weeks, before delivery, immediate postpartum, and 2–6 months postpuerperium. Results. Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 ( r = 0.50 ), insulin resistance index ( r = 0.26 ), and body mass index ( r = 0.28 ) and inversely correlated to C-reactive protein ( r = − 0.27 ). Chemerin levels were directly and strongly correlated with IL-10 ( r = 0.41 ) and interleukin-4 ( r = 0.50 ) and inversely correlated to insulin resistance index ( r = − 0.23 ) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups. Conclusion. AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.