Insulin resistance is an independent correlate of increased urine albumin excretion: a cross‐sectional study in Iranian Type 2 diabetic patients

Aims To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods Three hundred and sixty‐one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005–2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE ≥ 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA‐IR). Results HOMA‐IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA‐IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA‐IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA‐IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7–6.2)]. Conclusions In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA‐IR is an independent predictor of UAE.     

非糖尿病人群中补体C3、超敏C反应蛋白与胰岛素抵抗指数(HOMA2-IR)相关性分析

目的 观察非糖尿病人群血清补体C3、超敏C反应蛋白(hs-CRP)水平及其与胰岛素抵抗的关系.方法 纳入587例非糖尿病个体,测定体重、身高、血压、腰围、空腹血浆葡萄糖、血清胰岛素、血脂、补体C3及hs-CRP等,计算胰岛素抵抗指数(HOMA2-IR).以HOMA2-IR上四分位为切点划分胰岛素抵抗与非胰岛素抵抗.结果 胰岛素抵抗人群补体C3和hs-CRP显著高于非胰岛素抵抗人群.校正性别、年龄、BMI及腰围后,部分相关分析发现补体C3与HOMA2-IR显著正相关(r=0.19,P＜0.01).去除性别、年龄、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇和腰围的影响后,随着补体C3的升高发生胰岛素抵抗的危险增加3.78倍(OR=3.78,P＜0.05);而hs-CRP与胰岛素抵抗的发生无统计学意义.结论 在非糖尿病人群中,补体C3与胰岛素抵抗的相关性强于hs-CRP.

Abstract：

Objective To observe and compare the association of serum levels of of complement component 3(C3)and high-sensitive C-reactive protein(hs-CRP)with insulin resistance in non-diabetic subjects. Methods 587non-diabetic Chinese were recruited. Weight, height, blood pressure, waist circumference, fasting plasma glucose,fasting serum insulin, blood lipids, C3 and hs-CRP were measured. HOMA index(HOMA2-IR)was calculated.Insulin resistance was defined as the upper quartile of HOMA2-IR. Results C3 and hs-CRP were significantly higher in subjects with insulin resistance compared with subjects without insulin resistance. After controlling for age, gender,body mass index, and waist circumference, C3 was positively and significantly correlated with HOMA2-IR(r = 0.19,P＜0.01). As C3 increased, subjects were 3.78(OR= 3.78, P＜0.05)times more likely to suffer from insulin resistance, after adjustment for age, gender, systolic blood pressure, diastolic blood pressure, total cholesterol,triglycerides,high-density lipoprotein cholesterol, and waist circumference. However, hs-CRP was not significantly correlated with insulin resistance. Conclusions Serum complement component 3 has a more marked association with insulin resistance than hs-CRP in non-diabetic Chinese.     

Serum bicarbonate,anion gap and insulin resistance in the National Health and Nutrition Examination Survey

Aims Metabolic acidosis may contribute to the development of insulin resistance. To date, there have been no population‐based studies of acid‐base status and insulin resistance. We examined the cross‐sectional relations between serum bicarbonate, anion gap, and insulin resistance in a subset of healthy participants in the 1999–2000 and 2001–2002 National Health and Nutrition Examination Surveys. Methods We included 1496 adults without diabetes or other chronic diseases. Insulin sensitivity was estimated by an index based on fasting insulin and triglyceride levels (MFFM). Linear regression was used to adjust for age, race, body mass index, albumin and other factors. Sample weights were used to produce weighted regression parameters. Results Median values of bicarbonate, anion gap and fasting levels of insulin, triglycerides and glucose were 23 mmol/l, 12.5 mmol/l, 48 pmol/l, 1.08 mmol/l and 5.0 mmol/l, respectively. After multivariable adjustment, bicarbonate was positively associated and anion gap was inversely associated with MFFM (P < 0.01). Participants in the highest quartile of bicarbonate had fasting insulin 12.76 pmol/l lower [95% confidence interval (CI) 5.96, 19.55; P for trend < 0.01] than those in the lowest quartile. Participants in the highest quartile of anion gap had fasting insulin 4.39 pmol/l higher (95% CI 0.47, 8.31; P for trend < 0.01) than those in the lowest quartile. Conclusions Lower bicarbonate and higher anion gap are independently associated with insulin resistance. Further research is needed to elucidate the relations between organic acid production, insulin resistance, and the pathogenesis of Type 2 diabetes.     

Adiponectin and C-reactive protein in obesity, type 2 diabetes, and monodrug therapy

To learn more about the factors that regulate adipokines in diabetes, we examined fasting plasma concentrations of adiponectin and C-reactive protein (CRP) in well-characterized groups of age-matched individuals classified as: (1) type 2 diabetes; (2) impaired fasting glucose or mild diabetes (IFG/mild DM); (3) obese, matched for body mass index (BMI); and (4) non-obese. Diabetic subjects were also studied on no phamacologic treatment, after 3 months randomization to metformin or glyburide, and after 3 months crossover to the opposite drug. CRP decreased and adiponectin increased progressively between subjects in groups 1 through 4. CRP was significantly associated with percent (r = 0.45) and total (r = 0.50) fat, insulin sensitivity as S(I) (r = -0.39) or homeostasis model assessment of insulin resistance [HOMA (IR)] (r = -0.36), and hemoglobin A(1c) (HbA(1c)) (r = 0.41). The relationship of CRP to percent fat appeared to be logarithmic and log CRP varied with percent fat independent of gender. Adiponectin concentration was significantly associated with insulin sensitivity as S(I) (r = 0.55) or HOMA (IR) (r = -0.46). Adiponectin concentrations were higher among women overall (all groups included) but not in women classified as type 2 diabetes. Although mean adiponectin was higher in subjects classified as non-obese compared to obese, adiponectin, in sharp contrast to leptin (previously reported data) and to CRP, varied markedly when expressed as a function of adiposity. Multiple regression models confirmed the strong relationship of adiponectin to insulin sensitivity, as well as the relationships of CRP to adiposity and insulin sensitivity. Glyburide treatment of diabetes decreased CRP and did so even though body weight increased. We conclude that both CRP and adiponectin correlate strongly to S(I). CRP, in contrast to adiponectin, is far more dependent on adiposity. The relationship between CRP (like leptin) and gender depends on how CRP is expressed relative to adiposity. Our data raise the possibility that gender differences in adiponectin may be lost in diabetes. Finally, pharmacologic treatment of diabetes may modulate CRP independent of adiposity.     

A double‐blind,randomized, placebo‐controlled trial of the short‐term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy,middle‐aged,centrally obese men

Aim To determine the short‐term effect of vitamin D₃ supplementation on insulin sensitivity in apparently healthy, middle‐aged, centrally obese men. Subjects and methods A double‐blind randomized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged ≥ 35 years received three doses of vitamin D₃ (120 000 IU each; supplemented group) fortnightly or placebo (control group). Hepatic fasting insulin sensitivity [homeostasis model assessment (HOMA), quantitative insulin‐sensitivity check index, HOMA‐2], postprandial insulin sensitivity [oral glucose insulin sensitivity (OGIS)], insulin secretion (HOMA%B, HOMA2‐%B), lipid profile and blood pressure were measured at baseline and at 6 weeks’ follow‐up. Results Seventy‐one of the recruited subjects completed the study (35 in supplemented group, 36 in control group). There was an increase in OGIS with supplementation by per protocol analysis (P = 0.038; intention‐to‐treat analysis P = 0.055). The age‐ and baseline 25‐hydroxyvitamin D level‐adjusted difference in change in OGIS was highly significant (mean difference 41.1 ± 15.5; P = 0.01). No changes in secondary outcome measures (insulin secretion, basal indices of insulin sensitivity, blood pressure or lipid profile) were found with supplementation. Conclusion The trial indicates that vitamin D₃ supplementation improves postprandial insulin sensitivity (OGIS) in apparently healthy men likely to have insulin resistance (centrally obese but non‐diabetic).     

Both intrauterine growth restriction and postnatal growth influence childhood serum concentrations of adiponectin

OBJECTIVE: Insulin resistance has been linked to intrauterine growth restriction; adiponectin is a strong determinant of insulin sensitivity. We aimed at studying the contributions of birthweight and insulin sensitivity to circulating adiponectin in children born small for gestational age (SGA). DESIGN: Cross-sectional, hospital-based study dealing with insulin sensitivity in SGA children. PATIENTS: Thirty-two prepubertal children born SGA (age 5.4 +/- 2.9 years) and 37 prepubertal children born appropriate for gestational age (AGA, age 5.9 +/- 3.0 years). MEASUREMENTS: Serum levels of fasting glucose, serum lipids, insulin (immunometric assay) and adiponectin concentrations (ELISA) were assessed, and insulin resistance (IR) and insulin secretion (beta-cell) were calculated by the homeostasis model of assessment (HOMA). RESULTS: SGA children had similar HOMA-IR, HOMA-beta-cell and adiponectin concentrations than AGA children. However, in a separate analysis of subjects older than 3 years of age, SGA children showed higher HOMA-IR after adjusting for sex, age and body mass index (BMI) standard deviation score (SDS). Circulating adiponectin was higher in SGA children [adjusted means: 14.5 mg/l (95% CI 12.9-16.1) and 18.7 mg/l (95% CI 17.0-20.3) for AGA and SGA children, respectively; P < 0.0001]. Further analysis revealed that the group of overweight SGA (arbitrarily defined as being in the higher quartile for the BMI SDS distribution in the sample) had decreased serum concentrations of adiponectin, compared to lean SGA children [adjusted means: 12.9 mg/l (95% CI 9.3-16.5) vs. 19.0 (95% CI 16.8-21.3), respectively; P = 0.001]. In a multiple regression model, HOMA-IR and SGA status explained 35% and 15% of adiponectin variance, respectively. CONCLUSIONS: Prenatal growth restriction is associated with insulin resistance but relatively increased adiponectin concentrations, provided overweight does not ensue. The contributions of circulating adiponectin to the increased risks for developing insulin resistance and type-2 diabetes in formerly SGA subjects merit further studies.     

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children

Aims To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). Methods This cross‐sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 ± 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual‐energy X‐ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. Results After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history × tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Conclusions Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.     

Rosiglitazone improves insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus

Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-γ (PPARγ) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARγ is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6 ± 0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFT_max) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82 ± 1.94 vs. 2.01 ± 1.58), while BMI and SFT_max increased, and leptin (4.72 ± 3.77 vs. 5.69 ± 4.30 ng/ml) and adiponectin levels (7.54 ± 10.20 vs. 12.89 ± 10.13 μg/ml) increased. The increase in serum leptin correlated with an increase in SFT_max (r = 0.511, p < 0.001) and with a reduction in HOMA-IR (r = −0.368, p < 0.001). The correlation of Δleptin with ΔHOMA-IR and with ΔSFT_max was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.     

Differences in insulin sensitivity, pancreatic beta cell function and circulating adiponectin across glucose tolerance status in Thai obese and non-obese women

Although adiponectin levels are associated with obesity and insulin insensitivity, the role of adiponectin in the progression to diabetes in non-obese subjects is unclear. Therefore, 289 women aged 50–80 years without previous history of diabetes or impaired glucose tolerance (IGT) were studied. They were classified as normal glucose tolerance (NGT), IGT or diabetes based on WHO criteria. Insulin sensitivity (S) and beta cell function (B) indices were calculated using homeostasis model assessment (HOMA). In obese women with BMI ≥ 25 kg/m² (n = 161), there were declines in HOMA-%S (P < 0.001), HOMA-%B (P < 0.05) and circulating adiponectin (P < 0.001) across glucose tolerance status. In non-obese women with BMI < 25 kg/m² (n = 128), there was no significant change in HOMA-%S in women with IGT and diabetes as compared to women with NGT. However, HOMA-%B (P < 0.05) and serum adiponectin levels (P < 0.001) were significantly decreased across glucose tolerance. Serum adiponectin levels were correlated to HOMA-%S in both obese and non-obese women while negative correlations between circulating adiponectin and HOMA-%B were demonstrated only in obese women. We have demonstrated in the present study the predominant role of beta cell dysfunction as compared to that of insulin resistance in the deterioration of glucose tolerance in non-obese women. Circulating adiponectin appears to be inversely related to beta cell dysfunction in addition to insulin resistance only in obese women.     

Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian Indian adolescents

High-sensitivity C-reactive protein (hs-CRP) levels are closely associated with adiposity and predict coronary heart disease and type 2 diabetes mellitus. However, relationships of CRP to adiponectin and other markers of insulin resistance have been inadequately researched in children. We measured fasting serum levels of adiponectin, insulin, hs-CRP, and lipoproteins, and recorded the anthropometric profile and percentage of body fat (%BF; bioimpedance method) in 62 (36 normal weight, 26 overweight) healthy, urban, postpubertal Asian Indian males (aged 14 to 18 years). Serum levels of adiponectin were lower (P = not significant [NS]), whereas those of fasting insulin (P = .01) and hs-CRP (P = .02) were higher in overweight subjects. Adiponectin levels inversely correlated with body mass index (BMI; r = -0.26, P < .05), %BF (r = -0.24, P < .05), fasting insulin (r = -0.32, P < .05) and insulin resistance measured by the homeostasis model of assessment (HOMA-IR; r = -0.31, P < .05), but not with hs-CRP levels. Fasting insulin and hs-CRP levels correlated significantly with BMI, %BF, waist circumference (WC), waist-to-hip circumference ratio (W-HR), and triceps and subscapular skinfold thickness. The correlation of adiponectin with insulin sensitivity was independent of abdominal obesity, but became nonsignificant after controlling for BMI and %BF. Further, BMI was an independent predictor of adiponectin levels and the ratio of adiponectin and %BF was an independent predictor of fasting insulin levels. Although adiponectin levels did not correlate with hs-CRP levels, we observed dichotomous relationships of adiponectin and hs-CRP levels with generalized and abdominal obesity, respectively. We conclude that generalized obesity affects the adiponectin-insulin relationship in postpubertal Asian Indian males; however, the relationship of adiponectin with hs-CRP needs further evaluation.     

Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population

Aim: Our aim was to provide a quantitative analysis of the changes in the principal determinants of insulin sensitivity and secretion in relation to fasting plasma glucose (FPG) or 2‐h plasma glucose (2h PG) in a Chinese population with a wide range of glucose tolerance. Methods: A total of 5728 adults spanning the entire range of glucose tolerance were included. Insulin sensitivity was measured by Matsuda insulin sensitivity index (ISI_M) and homeostasis model assessment of 1/homeostasis model assessment of insulin resistance (HOMA‐IR). β‐Cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at early‐phase DI₃₀ and total DI₁₂₀. The exponential curve was established as the best fit for the relationship between insulin sensitivity or β‐cell function and FPG or 2h PG. Results: Relative to the trend classified as increasing 2h PG, hepatic insulin sensitivity and insulin secretion showed a decreasing trend to a substantial degree as FPG increased. A 1 mmol/l increase in FPG and 2h PG concentration was associated with a ?22 and ?21% decline in ISI_M, ?16 and ?4% in 1/HOMA‐IR, ?38 and ?35% in DI₃₀ and ?36 and ?26% in DI₁₂₀. The decay constant of ISI_M and DI₃₀ in IFG or ISI_M, 1/HOMA‐IR, DI₃₀ and DI₁₂₀ in IGT was lower than that in normal glucose tolerance. Significant interactions between sex and glucose levels determining DI were found. Conclusions: We conclude that impairment of insulin sensitivity and insulin secretion contributes to both FPG or 2h PG hyperglycaemia in a Chinese population, but that the decline in insulin secretion is more pronounced with increasing fasting than 2h PG.     

Prevalence and independent predictors of insulin resistance in children from Crete,Greece: The Children Study

Background It has been proposed that insulin resistance (IR) is associated with the development of Type 2 diabetes mellitus and cardiovascular disease. The aim of this study is to determine the prevalence of IR in Greek schoolchildren and to investigate factors associated with IR. Methods Between October 2005 and March 2006, 522 children were recruited from Crete. Physical activity and dietary habits, anthropometric and biochemical characteristics, as well as medical history of pupils’ parents were recorded. IR was estimated using the homeostasis model assessment (HOMA‐IR), fasting glucose‐to‐insulin ratio (FGIR) and quantitative insulin sensitivity check index (QUICKI). Multiple linear regression was used to determine independent predictors for IR. Results Fasting insulin levels and HOMA‐IR scores were higher in obese children and girls compared with their normal‐weight peers (P < 0.001). Moreover, the former had lower values in FGIR and QUICKI indices compared with the latter, indicating that obese children and girls are more insulin resistant compared with their counterparts (P < 0.001). The prevalence of IR was 9.2% (2.9% in normal‐weight, 10.5% in overweight and 31.0% in obese children), using as a threshold HOMA‐IR > 2.10 97.5th percentile of normal‐weight participants). Multiple linear regression revealed that central adiposity, female gender and intake of simple carbohydrates is associated positively with HOMA‐IR values, even after controlling for many other factors. Conclusion These findings demonstrate that girls and obese children, particularly those with central adiposity, are at high risk of developing IR. Therefore, these groups should be targets of Type 2 diabetes mellitus and cardiovascular disease preventive interventions.     

Circulating adiponectin levels and risk of type 2 diabetes in the Japanese

Background:

Adiponectin has anti-inflammatory and insulin-sensitizing properties. Prospective studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels.

Objective:

We examined prospectively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers, taking visceral fat mass into account.

Subjects and methods:

Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008; had biochemical data including serum adiponectin; were free of diabetes at baseline; and received health screening in 2011. Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects, as well as subgroups. Stratified analyses were carried out according to variables including visceral fat area (VFA).

Results:

During 3 years of follow-up, 217 diabetic cases were newly identified. Of these, 87% had a prediabetes at baseline. Serum adiponectin level was significantly, inversely associated with incidence of diabetes, with odds ratios (95% confidence interval) adjusted for age, sex, family history, smoking, alcohol drinking, physical activity and body mass index (BMI) for the lowest through highest quartile of adiponectin of 1 (reference), 0.79 (0.55–1.12), 0.60 (0.41–0.88) and 0.40 (0.25–0.64), respectively (P-value for trend <0.01). This association was materially unchanged with adjustment for VFA instead of BMI. After further adjustment for both homeostasis model assessment of insulin resistance and hemoglobin A1c, however, the association became statistically nonsignificant (P-value for trend=0.18). Risk reduction associated with higher adiponectin levels was observed in both participants with and without obesity or insulin resistance at baseline.

Conclusions:

Results suggest that higher levels of circulating adiponectin are associated with a lower risk of type 2 diabetes, independently of overall and intra-abdominal fat deposition, and that adiponectin may confer a benefit in both persons with and without insulin resistance.     

Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations

Aims/hypothesis Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. Several reports suggest that genetic variants in the adiponectin gene are associated with circulating levels of adiponectin, insulin sensitivity and type 2 diabetes risk. Recently two receptors for adiponectin have been cloned. Genetic studies have yielded conflicting results on the role of these genes and type 2 diabetes predisposition. In this study we aimed to evaluate the potential role of genetic variation in these genes in syndromes of severe insulin resistance, type 2 diabetes and in related metabolic traits in UK Europid populations. Materials and methods Exons and splice junctions of the adiponectin receptor 1 and 2 genes (ADIPOR1; ADIPOR2) were sequenced in patients from our severe insulin resistance cohort (n=129). Subsequently, 24 polymorphisms were tested for association with type 2 diabetes in population-based type 2 diabetes case–control studies (n=2,127) and with quantitative traits in a population-based longitudinal study (n=1,721). Results No missense or nonsense mutations in ADIPOR1 and ADIPOR2 were detected in the cohort of patients with severe insulin resistance. None of the 24 polymorphisms (allele frequency 2.3–48.3%) tested was associated with type 2 diabetes in the case–control study. Similarly, none of the polymorphisms was associated with fasting plasma insulin, fasting and 2-h post-load plasma glucose, 30-min insulin increment or BMI. Conclusions/interpretation Genetic variation in ADIPOR1 and ADIPOR2 is not a major cause of extreme insulin resistance in humans, nor does it contribute in a significant manner to type 2 diabetes risk and related traits in UK Europid populations. Electronic supplementary material The online version of this article () contains supplementary material, which is accessible to authorised users.     

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate—eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118–125) vs. 114 (108–120) mmHg; P = 0.01] and diastolic [73 (66–80) vs. 67 (70–73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1–9.9) vs. 7.5 (7.2–8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61–3.20) vs. 0.49 (0.31–0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.     

Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

Aims/hypothesis Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear.Subjects and methods Combining euglycaemic–hyperinsulinaemic clamp studies with indirect calorimetry and skeletal muscle biopsies, we examined the relationship between plasma adiponectin and parameters of whole-body glucose and lipid metabolism, and muscle glycogen synthase (GS) activity in 51 Caucasians (ten lean, 21 obese and 20 with type 2 diabetes).Results Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes. Plasma adiponectin was positively associated with insulin-stimulated glucose disposal (r=0.48), glucose oxidation (r=0.54), respiratory quotient (r=0.58) and non-oxidative glucose metabolism (r=0.38), and negatively associated with lipid oxidation during insulin stimulation (r=−0.60) after adjustment for body fat (all p<0.01). Most notably, we found a positive association between plasma adiponectin and insulin stimulation of GS activity in skeletal muscle (r=0.44, p<0.01).Conclusions/interpretation Our results indicate that plasma adiponectin may enhance insulin sensitivity by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes.     

Ⅱ型糖尿病血清超敏C-反应蛋白与胰岛素抵抗的关系

目的探讨血清CRP与胰岛素抵抗之间的相关性及其临床意义。方法Ⅱ型糖尿病患者122例,测定其血清超敏CRP、空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、胆固醇(TCH)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)、尿酸(UA)、糖化血红蛋白(HbA1c)等生化指标。并测定每个病人的血压(收缩压SBP,舒张压DBP),体重指数(BMI)。计算胰岛素抵抗(IR)和胰岛素敏感指数(ISI)。结果高CRP组SBP、DBP、TG、BMI均显著高于正常CRP组(P<0.05),而高CRP组的HDL-C则显著低于正常CRP组(P<0.01)。血清超敏C-反应蛋白与各项指标之间的相关性分析表明,糖尿病病人血清hs-CRP与DBP、BMI、FPG、FINS、TG、UAI、R均存在显著正相关(P<0.05或P<0.01),hs-CRP与HDL-CI、SI之间则存在显著负相关(P<0.05)。结论糖尿病病人血清超敏CRP与胰岛素抵抗之间存在较好的相关性,CRP在糖尿病发生及发展中起一定的作用,超敏CRP可作为Ⅱ型糖尿病的一个早期协助诊断指标。     

Supplementation with<Emphasis Type="Italic"> trans</Emphasis>10<Emphasis Type="Italic">cis</Emphasis>12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity

Aims/hypothesis Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insulin resistance in obese men, we used this fatty acid to investigate the effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations, including their associations with change in insulin sensitivity.Methods We randomised (double-blind) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin sensitivity (hyperinsulinaemic–euglycaemic clamp), intact proinsulin, insulin, the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed before and after supplementation.Results Supplementation with t10c12CLA increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C-peptide concentrations (p<0.001) in comparison with control subjects. Adiponectin, however, did not change significantly. The change in proinsulin, but not the proinsulin : insulin ratio, was related to impaired insulin sensitivity (r=–0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose, adiponectin and BMI. Conversely, the correlation between insulin sensitivity and specific insulin (r=–0.46, p<0.001) did not remain significant after adjustment for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin concentrations (r=–0.34, p<0.01).Conclusions/interpretation In obese men, t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity, independently of changes in insulin concentrations. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular disease. The use of weight-loss supplements containing this fatty acid is worrying.Abbreviations ANCOVA analysis of covariance - CLA conjugated linoleic acid - t10c12 trans10cis12     

Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01–0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.