Fatty liver index and mortality: the Cremona study in the 15th year of follow-up

A fatty liver, which is a common feature in insulin-resistant states, can lead to chronic liver disease. It has been hypothesized that a fatty liver can also increase the rates of non-hepatic-related morbidity and mortality. Therefore, we wanted to determine whether the fatty liver index (FLI), a surrogate marker and a validated algorithm derived from the serum triglyceride level, body mass index, waist circumference, and γ-glutamyltransferase level, was associated with the prognosis in a population study. The 15-year all-cause, hepatic-related, cardiovascular disease (CVD), and cancer mortality rates were obtained through the Regional Health Registry in 2011 for 2074 Caucasian middle-aged individuals in the Cremona study, a population study examining the prevalence of diabetes mellitus in Italy. During the 15-year observation period, 495 deaths were registered: 34 were hepatic-related, 221 were CVD-related, 180 were cancer-related, and 60 were attributed to other causes. FLI was independently associated with the hepatic-related deaths (hazard ratio = 1.04, 95% confidence interval = 1.02-1.05, P < 0.0001). Age, sex, FLI, cigarette smoking, and diabetes were independently associated with all-cause mortality. Age, sex, FLI, systolic blood pressure, and fibrinogen were independently associated with CVD mortality; meanwhile, age, sex, FLI, and smoking were independently associated with cancer mortality. FLI correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (Spearman's ρ = 0.57, P < 0.0001), and when HOMA-IR was included in the multivariate analyses, FLI retained its association with hepatic-related mortality but not with all-cause, CVD, and cancer-related mortality. CONCLUSION: FLI is independently associated with hepatic-related mortality. It is also associated with all-cause, CVD, and cancer mortality rates, but these associations appear to be tightly interconnected with the risk conferred by the correlated insulin-resistant state.     

Contrasting associations of insulin resistance with diabetes,cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

Aims/hypothesis

Insulin resistance is commonly proposed as a precursor to both type 2 diabetes and cardiovascular disease (CVD), yet few studies have directly compared insulin resistance with both outcomes simultaneously and determined whether associations with each outcome differ in strength or are comparable. We assessed the association of fasting insulin and HOMA-IR with incident CVD and diabetes in older people.

Methods

In the long-term follow-up of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) cohort, HOMA-IR measurement was available in 4,742 older people (70–82 years) without diabetes at baseline. Of these, 283 developed diabetes during the 3.2 year within-trial follow-up, while 1,943 all-cause deaths, 470 CHD deaths (identified from death records) and 590 fatal/non-fatal CVD events (identified from medical record linkage in the Scottish participants) occurred during an extended 8.6 years of total follow-up. Cause-specific Cox proportional-hazards models were fitted using multivariable models.

Results

Higher HOMA-IR was associated with incident diabetes: HR 4.80 (95% CI 3.14, 7.33) comparing extreme thirds after adjustment for confounders. However, HOMA-IR in the top third was not associated with all-cause mortality, CHD mortality or fatal/non-fatal CVD: HR 1.02 (95% CI 0.90, 1.17), 1.03 (0.79, 1.36) and 0.94 (0.74, 1.20), respectively. Results were similar when fasting insulin was considered as an exposure.

Conclusions/interpretation

Our data support insulin resistance as a predictor of diabetes in later life but, perhaps surprisingly, suggest this pathway is of negligible importance to CVD outcomes in the elderly.     

Novel adipokines vaspin and irisin as risk biomarkers for cardiovascular diseases in type 2 diabetes mellitus

Aims

Vaspin and irisin are novel cytokines proposed as potential new biomarkers of insulin resistance and endothelial dysfunction. This work is to investigate circulating levels of vaspin and irisin in patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease (CVD) to study potential association with disease risk.

Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss

Aims/hypothesis

Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss.

Methods

Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, ??-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6?month plasma samples from 500 participants who had lost ??4?kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (?HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n?=?22).

Results

Mean weight loss was 8.67?±?4.28?kg; mean ?HOMA-IR was ?0.80?±?1.73, range ?28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r?=?0.50, p?p?r?=?0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ?HOMA-IR (p?=?0.007).

Conclusions/interpretation

A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.     

Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance

CONTEXT: Adipose tissue-derived adipokines may contribute to insulin resistance. OBJECTIVE: We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes). DESIGN, SETTING, AND PARTICIPANTS: We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998-2001) of the Framingham Offspring Study. We measured levels of glucose, insulin, adiponectin, resistin, and TNFalpha in fasting blood samples and defined metabolic syndrome by updated National Cholesterol Education Program criteria. We used ANOVA to test associations of adipokines with insulin resistance and multivariable logistic regression models to assess joint associations of adipokines and metabolic syndrome with insulin resistance. MAIN OUTCOME MEASURE: Homeostasis model (HOMA-IR), with insulin resistance defined by HOMA-IR greater than the 75th percentile, was measured. RESULTS: Age- and sex-adjusted HOMA-IR levels were inversely related to adiponectin (r = -0.40, P < 0.0001) and positively related to resistin (r = 0.13, P < 0.0001) and TNFalpha (r = 0.12, P < 0.0001). The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFalpha (from 18.8 to 32.0%; P < 0.0001). Results were similar after adjustment for body mass index. These associations were present in individuals with or without the metabolic syndrome. In multivariable regression models, metabolic syndrome and adipokines individually and jointly were significantly associated with insulin resistance. CONCLUSION: Adverse levels of adipokines are associated with insulin resistance in individuals at low or high diabetes risk.     

Relation of plasma ceramides to visceral adiposity,insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study

Aims/hypothesis

Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort.

Methods

A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed.

Results

The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m². Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p?<?0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β?=?0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β?=??0.14 to ?0.16, p?<?0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β?=?0.08 to 0.09, p?<?0.001) and inversely with polyunsaturated ceramides (β?=??0.06 to ?0.07, p?<?0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors.

Conclusions/interpretation

Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

     

Diabetes mellitus and mortality from all-causes,cancer, cardiovascular and respiratory disease: Evidence from the Health Survey for England and Scottish Health Survey cohorts

BackgroundDiabetes mellitus is associated with differing rates of all-cause and cause-specific mortality compared with the general population; although the strength of these associations requires further investigation. The effects of confounding factors, such as overweight and obesity and the presence of co-morbid cardiovascular disease (CVD), upon such associations also remain unclear. There is thus a need for studies which utilise data from nationally-representative samples to explore these associations further.MethodsA cohort study of 204,533 participants aged 16 + years (7,199 with diabetes) from the Health Survey for England (HSE) (1994–2008) and Scottish Health Survey (SHeS) (1995, 1998 and 2003) linked with UK mortality records. Odds ratios (ORs) of all-cause and cause-specific mortality and 95% confidence intervals were estimated using logistic and multinomial logistic regression.ResultsThere were 20,051 deaths (1,814 among those with diabetes). Adjusted (age, sex, and smoking status) ORs for all-cause mortality among those with diabetes was 1.68 (95%CI 1.57–1.79). Cause-specific mortality ORs were: cancer 1.26 (1.13–1.42), respiratory diseases 1.25 (1.08–1.46), CVD 1.96 (1.80–2.14) and ‘other’ causes 2.06 (1.84–2.30). These were not attenuated significantly after adjustment for generalised and/or central adiposity and other confounding factors. The odds of mortality differed between those with and without comorbid CVD at baseline; the ORs for the latter group were substantially increased.ConclusionsIn addition to the excess in CVD and all-cause mortality among those with diabetes, there is also increased mortality from cancer, respiratory diseases, and ‘other’ causes. This increase in mortality is independent of obesity and a range of other confounding factors. With falling CVD incidence and mortality, the raised risks of respiratory and cancer deaths in people with diabetes will become more important and require increased health care provision.     

Contribution of visceral adiposity and insulin resistance to metabolic risk factors in Japanese men

We investigated the relative impacts of visceral adiposity and insulin resistance on the metabolic risk profile in middle-aged Japanese men. A cross-sectional study was conducted in 636 nondiabetic Japanese men with a mean age of 51.6 years. Visceral adipose tissue (AT) was assessed using computed tomography, and insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic risk factors were diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria: (1) hypertriglyceridemia, (2) low high-density lipoprotein cholesterol, (3) hypertension, (4) impaired fasting glucose, and (5) impaired glucose tolerance. Visceral AT and HOMA-IR were significantly and positively correlated with each other (r = 0.41, P < .001). Using the 75th percentile value as a cut point, those with isolated large visceral AT showed significantly greater odds ratios for each of the 5 risk factors measured except impaired fasting glucose, whereas those with isolated high HOMA-IR showed significantly greater odds ratios for each of the 5 risk factors except hypertriglyceridemia and impaired glucose tolerance, compared with the control group. The combined group (increased visceral AT and HOMA-IR) had the highest odds ratios for all studied risk factors. On logistic regression analysis using visceral AT and HOMA-IR as continuous independent variables, they were each independently associated with most of the metabolic risk factors and their clustering. In conclusion, neither visceral AT nor HOMA-IR stands out as the sole driving force of the risk profile; each makes a significant contribution to metabolic abnormalities in Japanese men.     

The relationship between body fat distribution and renal damage in Chinese with obesity.

OBJECTIVE: It has been recognized that in addition to being overweight, abnormal fat distribution may be associated with the etiology of metabolic syndrome. Asian people are more prone to develop visceral obesity than people in western countries. The present study was initiated to evaluate the relationship between visceral obesity and renal damage in Chinese obese people. METHODS: As measured by computed tomography, the areas of visceral fat were compared between 30 patients with biopsy-proven obesity-related glomerulopathy (ORG) and 20 obese volunteer controls that were free of renal diseases. The two groups were matched for age and sex. RESULTS: It was found that the areas of visceral fat were markedly increased in patients with ORG, while body mass indexes were similar in the two groups. Patients with ORG also showed higher levels of total cholesterol and a higher degree of insulin resistance than the controls. Multiple logistic regression analysis revealed that visceral obesity was significantly associated with the prevalence of ORG (OR 1.136; 95%CI, 1.106-1.166; P=0.003). Interestingly, proteinuria level was related directly with waist circumference, visceral obesity and levels of total cholesterol, fasting glucose, insulin and HOMA-IR ( P<0.05). Moreover, only HOMA-IR was independently associated with proteinuria level in stepwise linear regression ( R=0.641; P=0.001). CONCLUSIONS: The present study illustrated the positive association between visceral obesity and ORG and between insulin resistance and proteinuria level in Chinese obese subjects.     

Psychological distress,cardiovascular complications and mortality among people with screen-detected type 2 diabetes: follow-up of the ADDITION-Denmark trial

Aims/hypothesis

The aim of this study was to examine the association between psychological distress and the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with screen-detected type 2 diabetes mellitus. In addition, we explored whether or not metabolic control and medication adherence could explain part of this association.

Methods

A follow-up study was performed including 1,533 patients aged 40–69 years with screen-detected type 2 diabetes mellitus identified in general practice during 2001–2006 in the Denmark arm of the ADDITION (Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care) study. Mental health was measured at baseline with the Mental Health Inventory 5 (MHI-5). Psychological distress was defined as an MHI-5 score of ≤68 (18.2% of the population). CVD risk factors were measured at baseline and repeated at the follow-up examination. Information on death, hospital discharge diagnosis, and antihypertensive and lipid-lowering drug treatment was obtained from national registers. Cox proportional regression was used to estimate HRs for the association between psychological distress, CVD events and all-cause mortality. Age- and sex-adjusted risk difference analyses were performed to estimate differences in meeting treatment targets.

Results

Patients with psychological distress had a 1.8-fold higher mortality rate (HR 1.76, 95% CI 1.23, 2.53) and a 1.7-fold higher risk of having a CVD event (HR: 1.69, 95% CI 1.05, 2.70) compared with those with an MHI-5 score of >68. Overall, psychological distress was not associated with the ability to meet treatment targets for HbA_1c levels, cholesterol levels or BP, or to redeem antihypertensive or lipid-lowering drug treatment.

Conclusions/interpretation

In people detected and treated early in the diabetes disease trajectory, those with psychological distress at the time of diagnosis had a higher risk of CVD events and death than those without psychological distress.     

The metabolic syndrome

Metabolic syndrome represents a cluster of clinical, biochemical and humoral abnormalities associated with impaired insulin action in glucose metabolism. In the literature also the term syndrome of insulin resistance, dysmetabolic syndrome X, Reaven syndrome or Kaplans dead quartet can be found. Hyperinsulinaemia, central obesity, essential hypertension, dyslipidaemia, impaired glucose homeostasis or type 2 diabetes, hyperuricaemia, hypercoagulable state, endothelial dysfunction and increased markers of inflammation such as C-reactive protein, selectines, adhesion molecules, pro-inflammatory cytokines are the typical components of metabolic syndrome increasing the risk of cardiovascular complications. List of currently recognized clinical and biochemical manifestations continues to expand and include also non-alcoholic steatohepatitis, polycystic ovaric syndrome (PCOS), hyperhomocysteinaemia and others. No standard definition of metabolic syndrome has been routinely used. The WHO initially proposed a definition of metabolic syndrome in 1998, and more recently NCEP-ATP III provided a new working definition in 2001, which is more suitable for clinical practice. Prevalence of metabolic syndrome is very high, about 25-30% in Caucasians, depending on diagnostic criteria used. The clinical significance of metabolic syndrome is augmented by its association with increased and accelerated atherosclerosis. Whether IR predicts cardiovascular disease (CVD) independently of diabetes and other CVD risk factors is still a matter of controversy. Recently there is a growing evidence that metabolic syndrome increases also the risk of all-cause mortality and risk of certain tumors.     

Effects of atorvastatin on apelin, visfatin (nampt), ghrelin and early carotid atherosclerosis in patients with type 2 diabetes

To investigate the influence of atrovastatin treatment on carotid intima-media thickness (CIMT) and serum levels of novel adipokines, like apelin, visfatin (nampt), and ghrelin, in patients with type 2 diabetes mellitus (T2DM). 87 statin-free patients (50 males) with T2DM, aged 55–70, but without carotid atherosclerotic plaques were initially enrolled. CIMT was assayed in all participants by ultrasound. Patients were then treated with atorvastatin (10–80?mg) to target LDL?<100?mg/dl. Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), apelin, visfatin and ghrelin were measured at baseline and after 12?months. Atorvastatin treatment significantly improved lipid profile across with increased apelin (from 0.307?±?0.130?pg/ml to 1.537?±?0.427?pg/ml; P?<?0.001) and suppressed visfatin (from 21.54?±?10.14?ng/ml to 15.13?±?7.61?ng/ml; P?=?0.002) serum levels in our diabetic patients. Standard multiple regression analysis showed that the atorvastatin-induced increment in apelin was independently associated with changes in total cholesterol (β?=?–0.510, P?=?0.030) and LDL-cholesterol (β?=?–0.590, P?<?0.001) (R ²?=?0.449, P?=?0.014), while the reduction of visfatin concentration was independently associated with the change in hsCRP (β?=?0.589, P?<?0.001; R ²?=?0.256, P?=?0.006), after adjustment for age, sex and BMI. CIMT and ghrelin did not alter significantly after 12?months of atorvastatin treatment (NS). Among participants, high-dose (80?mg) rather than low-dose (10?mg) of atorvastatin treatment yielded greater (P?<?0.05) changes in apelin, visfatin and CIMT levels despite the final equivalent levels of LDL. Atorvastatin administration increased apelin and decreased visfatin serum levels significantly, without change of CIMT, in patients with T2DM. However, high-dose of atorvastatin exerted more favourable impact on adipokines and CIMT than low-dose. Our results implicate another important link between adiposity and atherosclerosis.     

The Effect of HMG-CoA Reductase Inhibitor on Insulin Resistance in Patients Undergoing Peritoneal Dialysis

Background

Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease (ESRD). Although statins exert pleiotropic effects, it is uncertain whether statin therapy improves insulin resistance in these patients. In this prospective randomized controlled trial, we aimed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis (PD).

Methods

Patients were randomized into a statin group (n?=?35) or a control group (n?=?35). The statin group received 10?mg per day of rosuvastatin for 6?months. We determined insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) index. Serum concentrations of adipokines such as adiponectin, leptin, and resistin were measured using enzyme-linked immunosorbent (ELISA) assay. As inflammatory markers, high sensitive C-reactive protein (hsCRP) and interleukin-6 were also measured.

Results

There were no significant differences in baseline characteristics between the two groups. Compared to baseline value, statin treatment significantly decreased HOMA-IR index from 2.37?±?1.08 to 2.05?±?0.82 (P?=?0.014). There was a concordant decrease in hsCRP levels in the statin group (2.05?±?1.57 to 1.21?±?0.84?mg/L, P?<?0.001), but such improvements were not observed in the control group. When between-group differences in these parameters were compared, hsCRP levels were more decreased in the statin group than in the control group (P?=?0.021 for between-group difference), whereas HOMA-IR index was not (P?=?0.189 for between-group difference). During this period, statin treatment did not result in the improved adipokine profiles.

Conclusion

This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment. Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients.     

Relation of the number of metabolic syndrome risk factors with all-cause and cardiovascular mortality

The metabolic syndrome (MS) is a constellation of risk factors associated with diabetes and cardiovascular disease. This syndrome consists of at least 3 parameters assessing central obesity, hypertension, high-density lipoprotein cholesterol, triglycerides, and impaired glucose metabolism. Whether persons with 4 or 5 risk factors are at higher risk than those with 3 risk factors is unclear. Also unclear is whether those without the MS but with 1 or 2 risk factors warrant therapy. We assessed cardiovascular and all-cause mortality as a function of the number of these risk factors. We followed 30,365 men for a median follow-up of 13.6 years. During follow-up, 1,449 participants died, 527 from cardiovascular causes. All of the individual parameters defining the MS were significantly associated with both all-cause and cardiovascular mortality (p <0.001). After adjustment for age and the other MS variables, hypertension was the most potent risk factor whereas central obesity and hypertriglyceridemia remained associated with both all-cause and cardiovascular mortality. A highly significant trend was also noted between both all-cause or cardiovascular mortality and the number of risk factors (p <0.001 for trend). Risk increased incrementally, beginning at 1 risk factor for cardiovascular mortality and at 2 risk factors for all-cause mortality. In conclusion, there is a continuum of risk as the number of metabolic syndrome risk factors increases. These findings add to the growing evidence that central obesity can independently and adversely affect health.     

The association of tumor necrosis factor α receptor 2 and tumor necrosis factor α with insulin resistance and the influence of adipose tissue biomarkers in humans

Tumor necrosis factor α (TNFα) is a proinflammatory adipokine hypothesized to link obesity with insulin resistance. Functional studies suggest that TNFα acts through pathways involving adipokines and fatty acids to induce insulin resistance. We tested the hypothesis that the association of measures of TNFα activity with insulin resistance is independent of obesity and adipose tissue biomarkers. We analyzed data from 2131 participants (without diabetes) of the Framingham Offspring Study examination 7. The outcome of interest was insulin resistance, measured using the homeostasis model assessment (HOMA-IR). Tumor necrosis factor α activity was measured by plasma tumor necrosis factor α receptor 2 (TNFr2) or TNFα; possible confounders included adipose tissue biomarkers (plasma adiponectin, resistin, and triglycerides). We used multivariable age- and sex-adjusted linear regression analyses to adjust for waist circumference and for biomarkers individually and simultaneously, and in biomarker-stratified (above and below median) models. We found that TNFr2 was positively associated with HOMA-IR (r = 0.21, P < .0001). In age- and sex-adjusted model, for each increase of 1 standard deviation of TNFr2 (SD = 746 pg/mL), the log (HOMA-IR) value was increased by 0.11 units (P < .0001). Adjustment for waist circumference reduced the TNFr2 β-coefficient (by about 45%), but the association between TNFr2 and HOMA-IR remained significant (P < .0001). Tumor necrosis factor α receptor 2 was still associated to HOMA-IR after adding adiponectin, resistin, and triglycerides (individually and simultaneously). We found similar associations with plasma levels of TNFα. We conclude that, in a representative community sample, measures of TNFα activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers.     

The relation of leptin and insulin with obesity-related cardiovascular risk factors in US adults

Previous studies of leptin with cardiovascular disease (CVD) risk factors have been limited by clinical samples or lack of representation of the general population. This cross-sectional study, designed to examine whether leptin or insulin may mediate the endogenous relation of obesity with metabolic, inflammatory, and thrombogenic cardiovascular risk factors, included 522 men and 514 women aged ≥40 years who completed a physical examination during the third National Health and Nutrition Examination Survey. Participants were free of existing CVD, cancer (except non-melanoma skin cancer), diabetes, or respiratory disease. In multivariable analyses adjusted for race/ethnicity and lifestyle factors, waist circumference (WC) was positively associated with blood pressure, triglyceride, LDL cholesterol, total cholesterol:HDL ratio, apolipoprotein B, C-reactive protein (CRP), and fibrinogen concentrations, and negatively associated with HDL cholesterol and apolipoprotein A1 levels. The associations of WC with the metabolic CVD risk factors were largely attenuated after adjustment for insulin levels, while the associations of WC with the inflammatory and thrombogenic factors (CRP and fibrinogen, respectively) were largely explained by adjustment for leptin concentrations. However, leptin levels were not independently associated with CRP and fibrinogen in men and CRP in women when adjusted for WC. Positive associations of leptin and insulin with fibrinogen in women, independent of WC, were noted. These results suggest that insulin may be an important mediator of the association of obesity with metabolic but not inflammatory or thrombogenic CVD risk factors, while leptin does not appear to influence cardiovascular risk through a shared association with these risk factors. However, we cannot rule out the possibility that leptin and insulin influence cardiovascular risk in women through independent effects on fibrinogen concentrations.     

Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial

Background

Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent.

Overweight, obesity, and their associations with insulin resistance and β-cell function among Chinese: a cross-sectional study in China

The aim of this study was to evaluate the associations of body mass index (BMI) with insulin resistance and β-cell function in subjects with normal glucose tolerance. A cross-sectional study was carried out in Fujian province by multistratified sampling from July 2007 to May 2008. The sample consisted of 2931 subjects aged from 20 to 79 years. The questionnaires, physical examinations, and laboratory tests were obtained from all the participants. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to estimate insulin sensitivity, insulin secretion was assessed using the HOMA-β index, and β-cell function was quantified as the ratio of the incremental insulin to glucose responses over the first 30 minutes during the oral glucose tolerance test (ΔI30/ΔG30). Another measure was adjusted for insulin sensitivity as it modulates β-cell function ([ΔI30/ΔG30]/HOMA-IR). Associations of BMI with morbidities were estimated using multiple logistic regression analysis. Relationships of BMI to insulin resistance and β-cell function were assessed using multiple linear regression analysis and analysis of covariance. The age- and sex-adjusted prevalence of overweight and obesity was 23.04% (27.44% in men and 18.40% in women) and 2.65% (2.75% in men and 2.55% in women), respectively. After adjustment for covariables, BMI was independently associated with morbidity conditions; and there were increasing trend for odds ratios of morbidities across the BMI categories. There were independent differences for HOMA-IR, HOMA-β, and ΔI30/ΔG30 between the normal-weight, overweight, and obese groups except for (ΔI30/ΔG30)/HOMA-IR. Body mass index was significantly and independently associated with HOMA-IR, HOMA-β, and ΔI30/ΔG30 in the multiple linear regression analysis. Body mass index was an independent risk factor for hypertension, type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, as well as the indexes of insulin resistance and β-cell function. It is imperative that the whole society pay more attention to the identification and intervention of overweight and obesity to prevent obesity-related diseases at the very early stage.     

Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study

Aims/hypothesis

Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals.

Methods

We studied two prospective cohorts: the Framingham Offspring Study (n?=?2,023) and the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study (n?=?887) cohorts. Insulin resistance was estimated by HOMA-insulin resistance (HOMA-IR). We used logistic regression analysis to test the association between adiponectin and incident type 2 diabetes overall and in insulin-resistant vs insulin-sensitive individuals (defined by ?? vs <75th percentile of HOMA-IR).

Results

At baseline, Framingham??s participants were 60?±?9?years old and 56% were women; KORA??s participants were 63?±?5?years old and 49% were women. Type 2 diabetes incidence was 5.4% over 6.5?years (n?=?109) in Framingham and 10.5% over 8?years (n?=?93) in KORA. Lower adiponectin levels were associated with type 2 diabetes incidence in both cohorts. In insulin-resistant individuals, lower adiponectin levels were associated with higher risk of type 2 diabetes incidence (OR 1.60 [95% CI 1.10?C2.31] per SD decrease in Framingham, p?=?0.01; and OR 2.34 [95% CI 1.16?C4.73] in KORA, p?=?0.02); while this was not observed in insulin-sensitive individuals (OR 1.10 [95% CI 0.73?C1.67] in Framingham, p?=?0.64; and OR 1.34 [95%CI: 0.88?C2.03] in KORA, p?=?0.18).

Conclusions/interpretation

We conclude that lower adiponectin levels are associated with higher risk of type 2 diabetes in insulin-resistant but not in insulin-sensitive individuals. This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.     

Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients

Recent studies suggest that serum cystatin C level is not only a sensitive marker for renal dysfunction but also a predictive marker for cardiovascular disease (CVD). However, the mechanism of this connection is not fully understood. We aimed to determine whether insulin resistance or various biomarkers of cardiovascular risk have a role in the link between cystatin C and CVD in type 2 diabetes mellitus patients. Anthropometric measurements and biochemical studies including inflammatory biomarkers were performed in 478 patients with type 2 diabetes mellitus. The degree of insulin resistance was assessed by homeostasis model assessment (HOMA-IR) and indicators of metabolic syndrome. Estimated glomerular filtration rate (eGFR) was derived from the Modification of Diet in Renal Disease study equation. After adjusting for age, sex, body mass index, and eGFR, the cystatin C level increased significantly in proportion to the number of metabolic syndrome components present (1.08 ± 0.06, 1.19 ± 0.04, 1.20 ± 0.04, 1.23 ± 0.04, and 1.37 ± 0.06 mg/L; P < .0001); and HOMA-IR increased significantly in proportion to cystatin C quartiles (1.16 ± 0.15, 1.40 ± 0.13, 1.49 ± 0.13, and 2.00 ± 0.17; P < .0001) (means ± SE). Albumin-creatinine ratio, fibrinogen, uric acid, homocysteine, high-sensitivity C-reactive protein, and lipoprotein(a) all showed significant correlations with cystatin C that were generally higher than those with eGFR. Cystatin C level was independently associated with HOMA-IR (β = 0.0380, P = .0082), albumin-creatinine ratio (β = 0.0004, P < .0001), uric acid (β = 0.0666, P < .0001), and homocysteine (β = 0.0087, P = .0004). In conclusion, cystatin C level was significantly associated with insulin resistance and biomarkers reflecting inflammation independent of renal function. These components may have a role in addition to that of eGFR in explaining the link between cystatin C and CVD in type 2 diabetes mellitus patients.