Consumption of red and processed meat and refined grains for 4 weeks decreases insulin sensitivity in insulin-resistant adults: A randomized crossover study

BackgroundRed and processed meat and refined grains are associated with an increased risk of type 2 diabetes. Interventions are limited. We hypothesized that a diet high in red and processed meat and refined grains (HMD) would decrease insulin sensitivity compared to a diet high in whole grains, nuts, dairy and legumes with no red meat (HWD).MethodsForty-nine subjects without diabetes [15 men and 34 women, age, 35.6 ± 15.7 years, body mass index (BMI), 27 ± 5.9 kg/m²] underwent two 4-week weight-stable dietary interventions in a randomized crossover design. The insulin sensitivity index (ISI) was calculated from the last 30 min of a continuous low-dose insulin (25 mU/kg·h) and glucose (4 mg/kg·min) infusion test (LDIGIT _120–150min) at the end of each diet.ResultsThe population fell into two very discrete groups: those with a very low insulin response in the LDIGIT _120–150min on HMD (Group 1 < 56 pmol/L, n = 24), and those with relatively normal insulin responses (Group 2 > 56 pmol/L, n = 25). Group 2 had significantly higher insulin concentrations [(median and interquartile range) 153, 180 for HMD vs. 123, 149 pmol/L for HWD; P = 0.019] and glucose concentrations [(mean ± standard deviation) 7.4 ± 1.3 for HMD vs.6.7 ± 1.2 mmol/L for HWD; P = 0.05], resulting in a significantly decreased ISI [(median and interquartile range) 21.1, 34.2 for HMD vs. 31.6, 39.4 for HWD; P = 0.014] compared to HWD. Log ISI after HMD was significantly correlated with BMI (r = − 0.5; P = 0.009), fat mass (r = − 0.55; P = 0.004) and self-reported activity levels (r = − 0.45; P = 0.024).ConclusionsA dietary pattern high in red and processed meat and refined grains decreased insulin sensitivity compared to a dietary pattern high in whole grains, nuts, dairy products and legumes only in relatively insulin-resistant adults.     

The relative contributions of insulin resistance and beta cell failure to the transition from normal to impaired glucose tolerance varies in different ethnic groups

AimTo evaluate ethnic differences in the contribution of decline in insulin secretion and insulin sensitivity in impaired glucose tolerance (IGT).MethodsSeven hundred and eighteen subjects of Arab, Japanese and Mexican American decent received oral glucose tolerance test (OGTT) with plasma glucose and insulin measurement every 30 min. The Matsuda index of insulin sensitivity and the relation between incremental increase under plasma insulin to glucose curves during the OGTT (ΔI_0–120/ΔG_0–120) were calculated.ResultsNGT Japanese subjects had highest insulin sensitivity index (7.1 ± 4.6) and lowest insulin secretion index ((ΔI_0–120/ΔG_0–120 = 1.1 ± 0.9). Mexican Americans and Arabs had lower insulin sensitivity (4.1 ± 2.8 and 3.5 ± 2.3, respectively) and higher insulin secretion indices (2.2 ± 2.0 and 2.5 ± 2.5). IGT subjects in all ethnic groups had reduced insulin sensitivity and insulin secretion compared to NTG subjects. However, the reduction in insulin sensitivity was the largest in Mexican American (30%), the smallest in Arabs (11.5%) and intermediate in Japanese (23%). Conversely, the decrease in insulin secretion was the greatest in Arabs (80%), the smallest in Mexican Americans (41%) and intermediate in Japanese (55%).In a multivariate regression analysis model, the decline in insulin secretion was a stronger determinant of 2-h plasma glucose in Arabs than the reduction in insulin sensitivity while the opposite was observed in Mexican Americans and Japanese.ConclusionDifferences in insulin sensitivity and insulin secretion are present amongst different ethnic groups. The relative contributions of reduced insulin action and impaired insulin secretion are likely to contribute differentially to progression from NGT to IGT (and diabetes) in different ethnic groups.     

Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3 years in the RISC study: Interaction with weight gain

AimsThe importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little studied.MethodsIn an analysis of data from the European RISC study, sedentary time and time spent in activity of moderate or vigorous intensity were assessed by accelerometry at baseline in 313 men and 414 women, aged 30–60 years, with insulin sensitivity as measured by euglycaemic–hyperinsulinaemic clamp. Three years later, cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were available for 549 participants.ResultsIn cross-sectional analyses using baseline data, after adjusting for age, gender, recruitment centre and time spent in activity of moderate or vigorous intensity, significant unfavourable associations were observed between higher sedentary time with body weight, HDL cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin secretion (all P_trend < 0.002). Sedentary time remained significantly associated with insulin secretion after adjusting for insulin sensitivity (P_trend = 0.02). In longitudinal analyses, higher baseline sedentary time was associated with 3-year increases in fasting glucose, fasting insulin and the HOMA insulin-resistance index score for the 50% of the study population who increased their BMI by at least 0.3 kg/m² (all P_trend < 0.01); these relationships remained significant after adjusting for time spent in activity of moderate or vigorous intensity. The 3-year increase in insulin secretion was lower in those spending more time doing activity of moderate or vigorous intensity (P_trend = 0.03).ConclusionThese prospective data suggest that less sedentary behaviour may partly counteract some of the negative effects of increasing body weight on glucose–insulin homoeostasis.     

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome

ObjectivePolycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS).MethodsTwenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses.ResultsThis multiethnic, obese sample was matched by age (PCOS, 37 ± 6; MetS, 40 ± 6 years) and body mass index (BMI) (PCOS, 34.6 ± 5.1; MetS, 33.7 ± 5.2 kg/m²). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P = .02), essential amino acids (P = .03), the essential amino acid lysine (P = .02), and the lysine metabolite α-aminoadipic acid (P = .02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between groups were observed in concentrations of free fatty acids or vitamin D metabolites. Evaluation of the relationship of metabolites with clinical characteristics showed 1) negative associations of essential and BCAA with insulin sensitivity and sex hormone-binding globulin and 2) positive associations with homeostasis model of insulin resistance and free testosterone; metabolites were not associated with BMI or percent body fat.ConclusionsPCOS was associated with significant metabolic alterations not attributed exclusively to androgen-related pathways, obesity, or MetS. Concentrations of essential amino acids and BCAA are increased in PCOS, which might result from or contribute to their insulin resistance.     

The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes

AimGenome-wide association studies have shown that variation in the FTO gene predisposes to obesity and related traits that are common features of polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of FTO variation on obesity, insulin sensitivity, and metabolic and hormonal profiles in PCOS.MethodsWe examined 136 PCOS women (mean body mass index [BMI]: 28.28 ± 6.95 kg/m², mean age: 25.36 ± 5.48 years). Anthropometric measurement, euglycaemic–hyperinsulinaemic clamp and oral glucose tolerance tests and sex hormone assessments were performed. The study group was genotyped for the FTO rs9939609 polymorphism.ResultsBMI (29.0 ± 6.9 kg/m² vs 26.1 ± 6.8 kg/m²; P = 0.023), body weight (80.1 ± 20.7 kg vs 72.6 ± 20.2 kg; P = 0.048), fat mass (29.7 ± 1 6.6 kg vs 24.6 ± 17.7 kg; P = 0.045) and waist circumference (89.8 ± 16.7 cm vs 83.2 ± 17.1 cm; P = 0.028) were higher in carriers of at least one copy of the A allele. Differences in these parameters were more significant when comparing AA and TT homozygotes. Women with the AA genotype also had decreased insulin sensitivity (P = 0.025) and follicle-stimulating hormone (P = 0.036). In logistic-regression analyses, the association of the FTO gene polymorphism with insulin sensitivity was no longer significant when BMI was included in the model.ConclusionVariation in the FTO gene modifies weight, adiposity and other measures of obesity and insulin sensitivity in PCOS. The examined FTO gene variant appears to have a greater impact on obesity and related traits in PCOS than in other phenotypes. The effect on insulin sensitivity appears to be secondary to its influence on obesity and body fat.     

Effect of Exercise Therapy on Monocyte and Neutrophil Counts in Overweight Women

IntroductionIt has been well known that physical inactivity is associated with a significantly higher incidence of coronary artery disease. This study aimed to test our hypothesis that endurance aerobic exercise training has cardiovascular protective effects as a result of inhibiting inflammatory processes.MethodsForty-two overweight women [age, 53.4 ± 9.8 years; body mass index (BMI), 28.0 ± 2.8] received electric bicycle ergometer exercise therapy at the lactate threshold intensity for 30 to 60 minutes per day, 1 to 6 times per week for 6 weeks. The exercise training was performed within the possible load (exercise duration and frequency) for each subject.ResultsLeukocyte, monocyte, and neutrophil counts significantly decreased after the exercise therapy (P < 0.05). In simple regression analysis, percent changes in monocyte and neutrophil counts were correlated with percent changes in fasting triglyceride levels, insulin sensitivity index, BMI, and maximal oxygen uptake (VO₂max). In stepwise multiple regression analysis, the percent change in monocyte counts was associated with percent changes in fasting triglyceride and VO₂max (r² = 0.368, P < 0.001), and the percent change in neutrophil counts was associated with percent changes in insulin sensitivity index and BMI (r² = 0.292, P < 0.001).ConclusionsEndurance aerobic exercise training can influence some inflammatory processes. Furthermore, increased aerobic capacity may be antiinflammatory and have cardiovascular protective effects in overweight women.     

Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity

ObjectiveThis study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of β-cell function and/or insulin sensitivity and their combined product.Research design and methodsThirty-three patients with type 2 diabetes were investigated. Their β-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA_1c and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA_1c response.ResultsAfter 6 months, unadjusted HOMA-B increased from 33 ± 24% to 43 ± 23% (P = 0.0210), whereas there was no significant change in HOMA-S (from 58 ± 35% to 61 ± 40%). The hyperbolic product increased by a relative 70% (from 15 ± 7% to 22 ± 15%; P = 0.0055). Body mass index decreased from 32.2 ± 5.1 kg/m² to 31.0 ± 4.8 kg/m² (P < 0.0001) and HbA_1c from 8.8 ± 1.0% to 7.6 ± 1.2% (P < 0.0001). No change was observed in adiponectin concentrations. Higher baseline HbA_1c values were a significant predictor of therapeutic response.ConclusionExenatide significantly increased HOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved β-cell function rather than increased insulin sensitivity accounts for the bulk of HbA_1c reduction following 6 months of exenatide treatment.     

Discontinuation of hormone replacement therapy in young GH-treated hypopituitary women increases liver enzymes

ObjectiveHypopituitarism, often characterized by hypogonadism, is associated with central obesity, increased cardiovascular and endocrine morbidity and mortality. In Turner syndrome, which is also characterized by hypogonadism liver enzymes are often elevated, but readily suppressed by a short course of hormone replacement therapy (HRT). We investigated the effect of HRT on liver enzymes, lipid levels and measures of insulin sensitivity 26 in hypopituitary women.DesignWe studied 26 hypopituitary women (age 38.8 ± 11.0 (mean ± SD years), BMI 27.4 ± 5.1 kg/m²) during HRT and 28 days off therapy.MethodsWe measured liver enzymes, fasting levels of lipids, insulin and glucose as well as adiponectin and leptin levels. Body composition was assessed by means of anthropometry and bioimpedance.ResultsAlanine transaminase (ALT) and aspartate transaminase (AST) increased after discontinuation of HRT (ALT; treated: 22.3 ± 11.5 vs. untreated: 27.1 ± 11.1 (U/L) (P < 0.02); AST; treated: 20.4 ± 6.1 vs. untreated: 24.6 ± 8.9 (U/L) (P < 0.002)), whereas other liver function tests remained unchanged. Measures of insulin sensitivity and fasting lipids were also unaffected by HRT, whereas leptin levels decreased with cessation of HRT (leptin; treated: 23 (8–71) vs. untreated: 20 (8–64) (μg/L) (P < 0.0005)).ConclusionShort time discontinuation of HRT in young hypopituitary women increased liver enzymes, whereas measures of insulin sensitivity and lipid levels remained unchanged. We speculate that the estrogen component of HRT has beneficial effects on hepatic metabolism through various pathways. Further studies including liver imaging and with a time-dependent design are needed to clarify the role of HRT on liver enzyme levels, metabolic variables and liver fat content.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

Étude de la corrélation entre la sensibilité à l’insuline et les paramètres anthropométriques et métaboliques dans le diabète de type 2

AimThe aim of the study was to evaluate correlations between insulin sensitivity and insulinosecretion with anthropometric and metabolic parameters in type 2 diabetics.Materials and methodsWe conducted a cross-sectional study among patients with type 2 diabetes mellitus treated with oral antidiabetic medications. The evaluation of insulin resistance and insulinosecretion was based on the calculation of the HOMA-IR and HOMA-β indices.ResultsThe mean age for the 100 diabetes recruited was 56.4 ± 8.4 years. The mean body mass index (BMI) and waist circumference (WC) were 30.5 ± 5.7 kg/m² and 101.2 ± 11.9 cm respectively. The HOMA-IR and HOMA β indices were respectively 3.5 ± 2.8 and 48.9 ± 45.5. We have found a significantly positive correlation between HOMA-IR index and weight (r = 0.406, p < 10⁻³), BMI (r = 0.432, p < 10⁻³) and WC (r  =  0.412, p < 10⁻³). We noticed a significant negative correlation between HOMA β index and fasting glucose (r = −0.457, p < 10⁻³) and A1 C (r = −0.399, p < 10⁻³). A positive statistically significant correlation was noted between HOMA-IR and HOMA-β (r = 0.400, p < 10⁻³).ConclusionInsulin resistance is very related to overweight, especially the android distribution of fat hence the need for adequate management of this android obesity. It would also be interesting to evaluate the effects of weight loss on insulin resistance parameters.     

Risk of type 2 diabetes and cumulative excess weight exposure in the Framingham Offspring Study

AimMid-life obesity is associated with T2D risk. However, less is known about the cumulative effect of obesity during adulthood.MethodsFramingham Offspring Study participants who had an examination at 35 ± 2 years and were initially free of T2D were included in this study (N = 1026). A cumulative excess weight (CEW) score (year*kg/m²) was calculated until T2D diagnostic or the end of follow-up.ResultsEighty-four individuals (8.2%) developed T2D over 20 ± 6 years. Mean CEW scores were 118.0 ± 114.6 year*kg/m² in individuals who developed T2D and 30.2 ± 91.4 year*kg/m² in those who did not develop T2D (P < 0.01). T2D risk was doubled for each standard deviation increase in the CEW score (OR = 1.99 [1.64-2.40]; P < 0.001). However, CEW score was only significantly associated with T2D incidence for participants with a baseline BMI < 25 kg/m² (OR = 2.13 [1.36–3.36]; P < 0.001).ConclusionsAccumulating weight between the mid-thirties to the mid-fifties increases the risk of developing T2D. However, BMI in mid-thirties remains a stronger predictor of T2D risk.     

Pioglitazone-induced improvements in insulin sensitivity occur without concomitant changes in muscle mitochondrial function

AimsPioglitazone (Pio) is known to improve insulin sensitivity in skeletal muscle. However, the role of Pio in skeletal muscle lipid metabolism and skeletal muscle oxidative capacity is not clear. The aim of this study was to determine the effects of chronic Pio treatment on skeletal muscle mitochondrial activity in individuals with type 2 diabetes (T2D).Materials and MethodsTwenty-four participants with T2D (13 M/11F 53.38 ± 2.1 years; BMI 36.47 ± 1.1 kg/m²) were randomized to either a placebo (CON, n = 8) or a pioglitazone (PIO, n = 16) group. Following 12 weeks of treatment, we measured insulin sensitivity by hyperinsulinemic–euglycemic clamp (clamp), metabolic flexibility by calculating the change in respiratory quotient (ΔRQ) during the steady state of the clamp, intra- and extra-myocellular lipid content (IMCL and EMCL, respectively) by ¹H magnetic resonance spectroscopy (¹H-MRS) and muscle maximal ATP synthetic capacity (ATPmax) by ³¹P-MRS.ResultsFollowing 12 weeks of PIO treatment, insulin sensitivity (p < 0.0005 vs. baseline) and metabolic flexibility (p < 0.05 vs. CON) significantly increased. PIO treatment significantly decreased IMCL content and increased EMCL content in gastrocnemius, soleus and tibialis anterior muscles. ATPmax was unaffected by PIO treatment.ConclusionsThese results suggest that 12 weeks of pioglitazone treatment improves insulin sensitivity, metabolic flexibility and myocellular lipid distribution without any effect on maximal ATP synthetic capacity in skeletal muscle. Consequently, pioglitazone-induced enhancements in insulin responsiveness and fuel utilization are independent of mitochondrial function.     

Women with normal glucose tolerance and a history of gestational diabetes show significant impairment of β-cell function at normal insulin sensitivity

ObjectiveAlthough the nature of gestational diabetes mellitus (GDM) remains unclear, the condition is thought to be related primarily to insulin resistance, overweight and obesity. Most studies include women with a history of GDM and later carbohydrate metabolism abnormalities, while reports of women with previous GDM and subsequent normoglycaemia are scarce. The aim of this study was to assess insulin resistance and β-cell function in normoglycaemic women with a history of GDM.Materials and methodsThe study group included 199 women, aged 38.4 ± 6.6 years, diagnosed with GDM within the last 5–12 years [GDM(+)] and a control group of 50 comparable women in whom GDM was excluded [GDM(−)], according to WHO criteria. Blood glucose and insulin levels were measured at the beginning (fasting) and at 60 and 120 min of oral glucose tolerance tests. Indices of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) were calculated.ResultsNormoglycaemia was observed in 57% of GDM(+) and 88% of GDM(−) women (P = 0.0003). Diabetes was diagnosed in 13 (6.5%) GDM(+) women and in none of the GDM(−) women. Comparison of 113 normoglycaemic GDM(+) and 44 normoglycaemic GDM(−) women revealed significantly impaired β−cell function (HOMA-B%: 131.1 ± 51.1 vs 144.7 ± 47.1, respectively; P = 0.038) with similar normal body mass index (BMI) and no differences in HOMA-IR and HOMA-S%.ConclusionIn this study, more than half of the GDM(+) women were presented with normal glucose tolerance. However, despite normoglycaemia, women with a history of GDM were characterized by significantly impaired insulin secretion, but no signs of increased insulin resistance.     

The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients

Aim of workTo explore the influence of the presence of concomitant fibromyalgia (FM) on the evaluation of disease activity score assessing 28 joints (DAS28), clinical disease activity index (CDAI) and modified health assessment questionnaire (MHAQ) in Egyptian patients with rheumatoid arthritis (RA).Patients and methodsThis study included 50 female RA patients; out of which 25 had concomitant FM (RAF group), the other 25 RA patients who served as controls did not have concomitant FM (RA group). All patients were subjected to an assessment of disease activity using the DAS 28 and the CDAI and assessment of functional outcome using MHAQ score.ResultsThe mean DAS 28 was significantly higher in RAF than RA patients (5.6 ± 1.1 versus 4.5 ± 1.3, P = 0.009). Also, the mean CDAI score was significantly higher in the RAF group (mean 23.3 ± 12.1 versus 13.7 ± 11.0, P = 0.002). The difference was attributed to significantly higher subjective items such as Tender joint count (TJC) and patient’s global assessment of general health (VAS-GH) in the RAF group. Mean MHAQ score was also higher in the RAF group (0.7 ± 0.6 versus 0.31 ± 0.4, P = 0.006).ConclusionFM is related to worse scores on the DAS28, CDAI and MHAQ in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 and CDAI scores because it is related to higher scores independently of objective evidence of RA activity.     

Quality of life after Roux-en-Y gastric bypass and changes in body mass index and obesity-related comorbidities

AimDynamics of improvement in health-related quality of life (QoL) after bariatric surgery have never been fully assessed, and neither has the potential influence of body mass index (BMI) and comorbidity modification. The objective of this study was to investigate early and medium-term changes in QoL following Roux-en-Y gastric bypass (RYGB), and their relationship to BMI and comorbidity variations.MethodsA total of 71 obese subjects (80% women, mean age 42.1 ± 11.2 years, mean baseline BMI 47.6 ± 6.2 kg/m²) undergoing RYGB filled in QoL questionnaires (SF-36) before and 3, 6 and 12 months after surgery. QoL was assessed using repeated-measures Anova, with associations between its changes and changes in BMI and comorbidities (diabetes, hypertension, dyslipidaemia, sleep apnoea, knee pain) assessed by mixed-effects models.ResultsPhysical QoL scales (physical component summary, PCS) significantly increased over time (from 38.9 ± 9.3 to 52.6 ± 7.9; P < 0.001) as did other physical SF-36 scales (all P < 0.001), whereas mental QoL summary scale did not vary significantly (from 45.7 ± 9.5 to 48.6 ± 11.5; P = 0.072). Major changes in QoL occurred at 3 months after surgical intervention to reach values comparable to those in the general population. PCS was mostly associated with changes in either BMI or comorbidity status except for diabetes, dyslipidaemia and sleep apnoea.ConclusionResults show that improvements in physical QoL after RYGB are observed as early as 3 months after intervention, and are independently associated with weight loss and improvements in comorbidities.     

Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes

AimThe role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking.MethodsRenal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD).ResultsAfter the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m⁻² BSA to 86.9 ± 6.1 mL/min/1.73 m⁻² BSA (P = 0.026) and from 979 ± 107 μmol/min¹/m² BSA to 1205 ± 94 μmol/min¹/m² BSA (P = 0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r = 0.625, P = 0.017).ConclusionOur observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function.     

Predictors of insulin resistance in the obese with metabolic syndrome

BackgroundIn the obese, the metabolic syndrome (MetS) is assumed to reflect insulin resistance.ObjectiveTo determine the predictors of insulin resistance in obese subjects with MetS.DesignWe used the 90th percentile of the homeostasis model assessment (HOMA) to define insulin resistance in 4958 nondiabetic adults evaluated in the National Health and Nutrition Examination Surveys, 1999–2004, and compared the 373 obese subjects who were insulin-resistant (HOMA 9.52 ± 5.73) to a control group of 373 obese who had the highest sensitivity to insulin (HOMA 1.79 ± 0.44).MeasurementsMetS was present in 312 (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin-sensitive control group. Demographic, metabolic, and lifestyle variables were analyzed with logistic regression.ResultsIn a logistic model of insulin resistance given the presence of MetS, the significant predictors were triglycerides (P = 0.0021), body mass index (P = 0.0096), HDL-cholesterol (P = 0.0098), age (P = 0.0242) and smoking (P = 0.0366).LimitationsCross-sectional design prevents elucidation of causality for the association between insulin resistance and MetS.ConclusionsInsulin resistance is not an obligatory correlate of MetS in the obese. Its likelihood can be predicted by cigarette smoking and by the severity of obesity and dyslipidemia.     

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes.MethodsIn this study, 63 patients (age 59 ± 8.3 years, baseline A1c 6.8 ± 0.7%, diabetes duration 3.0 ± 2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR).ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P = 0.02), decreased HOMA-IR (P < 0.001), and reduced AUC_glucagon (P < 0.001). Of note, however, IIT had no significant impact on AUC_GLP-1 (P = 0.24) and reduced AUC_GIP (P = 0.02).ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.     

Heart failure and chronic kidney disease in a registry of internal medicine wards

BackgroundThe aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methodsWe used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.ResultsOf the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m²) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m²). Both groups were significantly older (P < 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 ± 86 vs. 125 ± 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m² increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).ConclusionHF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly.     

Improvement in diet habits,independent of physical activity helps to reduce incident diabetes among prediabetic Asian Indian men

AimsTo assess the beneficial effects of the components of lifestyle intervention in reducing incidence of diabetes in Asian Indian men with impaired glucose tolerance (IGT) in India.MethodsThis analysis was based on a 2 year prospective, randomized controlled primary prevention trial in a cohort of Asian Indian men with IGT (n = 537) (Clinical Trial No: NCT00819455). Intervention and control groups were given standard care advice at baseline. Additionally, the intervention group received frequent, mobile phone based text message reminders on healthy lifestyle principles. Dietary intake and physical activity habits were recorded by validated questionnaires. The lifestyle goals were: reductions in consumption of carbohydrates, oil, portion size and body mass index of at least 1 unit (1 kg/m²) from baseline and maintenance of good physical activity. The association between diabetes and lifestyle goals achieved was assessed using multiple logistic regression analyses. Changes in insulin sensitivity (Matsuda's insulin sensitivity index) and oral disposition index during the follow-up were assessed.ResultsAt the end of the study, 123 (23.8%) participants developed diabetes. The mean lifestyle score was higher in the intervention group compared with control (2.59 ± 1.13 vs. 2.28 ± 1.17; P = 0.002). Among the 5 lifestyle variables, significant improvements in the 3 dietary goal were seen with intervention. Concomitant improvement in insulin sensitivity and oral disposition index was noted. Higher lifestyle score was associated with lower risk of developing diabetes (odds ratio: 0.54 [95% CI: 0.44–0.70]; P < 0.0001).ConclusionsBeneficial effects of intervention were associated with increased compliance to lifestyle goals. The plausible mechanism is through improvement in insulin sensitivity and beta cell preservation.