Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity

Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377] Received: 3 August 2001 and in revised form: 26 November 2001     

单不饱和脂肪酸膳食通过缓解氧化应激改善糖耐量正常人群的胰岛素敏感性

20例健康受试者分别接受单不饱和脂肪酸饮食、多不饱和脂肪酸饮食、饱和脂肪酸饮食3d,单不饱和脂肪酸可以改善机体的氧化应激状态,从而改善胰岛素敏感性.     

Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women.

OBJECTIVE: The major aim was to study the relation between habitual dietary intake and glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women. Dietary intake was also compared between women with normal (NGT) or impaired glucose tolerance (IGT). DESIGN: Habitual dietary intake was studied using a modified diet history method, from which the energy, carbohydrate, fat and protein intake was calculated. Glucose tolerance was determined as the 2 h glucose value after a 75 g oral glucose tolerance test. Insulin sensitivity was studied with a euglycemic, hyperinsulinaemic clamp, whilst insulin secretion was measured as the acute (2-5 min) response to iv arginine (5 g) at fasting, 14 and >25 mmol L(-1) glucose. SETTING: Clinical research unit at the University Hospital in Malmo, Sweden. Subjects. A total of 74 women (mean+/-SD age 58.7+/-0.4 years). RESULTS: In the entire group, the 2 h glucose level correlated with polyunsaturated fat intake (PUFA, r = 0.41, P < 0.001), and negatively with carbohydrate intake (r = -0.23, P = 0.05). The relation between 2 h glucose and PUFA was independent of body fat content and insulin sensitivity in a multivariate model. Insulin sensitivity correlated with energy intake (r = 0.31, P = 0.007) and PUFA (r = -0.27. P = 0.022). However, these correlations were not significant after adjustment for body fat content in a multivariate model. There were no correlations between insulin secretory variables and habitual dietary intake. Of the 74 women, 60 had NGT and 14 had IGT. The NGT and IGT groups did not differ in intakes of total energy, carbohydrate or protein. The IGT women had higher intake of PUFA (P = 0.003), whilst the total, saturated and monounsaturated fat intake did not differ between the groups. CONCLUSION: Dietary parameters are not independently associated with insulin sensitivity or insulin secretion in postmenopausal women. Furthermore, dietary habits are largely similar in women with NGT and IGT, although subtle differences cannot be excluded due to the small study size. Therefore, habitual intake of total carbohydrate or total fat seems not to be the major determinant of glucose tolerance in nondiabetic Caucasian postmenopausal women.     

The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype

BACKGROUND: Inflammation is strongly related to obesity and the risk of cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n-3 polyunsaturated fatty acid (PUFA) may be attributable to its anti-inflammatory properties. OBJECTIVE: To investigate whether an individual's habitual inflammatory status influences the impact of a LC n-3 PUFA intervention on CVD risk. DESIGN: The study was a randomized crossover design. Subjects received LC n-3 PUFA capsules or a placebo for 12 weeks, with 4-week washout between phases. Thirty women, in the top and bottom tertiles of baseline sialic acid concentration, formed raised inflammatory status (top, n = 12) and reference (bottom, n = 18) groups. Baseline data were analysed using one-way anova, differences between treatment phases were calculated at each timepoint and analysed using a random effects model. RESULTS: At baseline, the raised inflammatory status group had significantly higher body mass index and area under the curve (AUC) insulin than the reference group. With LC n-3 PUFA supplementation, both groups showed significantly higher plasma eicosapentaenoic acid and docosahexaenoic acid at 4 and 12 weeks (p < 0.001), and lower triacylglycerols (4 weeks p < 0.01 and 12 weeks p < 0.05). The difference in AUC insulin between the two treatment phases at 12 weeks was significantly greater in the raised inflammatory status group compared to the reference group (p < 0.05). Inflammatory markers were significantly lower after 12 weeks LC n-3 PUFA supplementation compared to baseline (C-reactive protein p < 0.05 and interleukin-6 p < 0.01), but there was no significant group effect. CONCLUSIONS: Habitual inflammatory status influences the impact of LC n-3 PUFA supplementation, but it is not clear whether the effect of LC n-3 PUFA on AUC insulin is mediated through inflammatory mechanisms.     

Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans

Aims/hypothesis Prolonged elevation of plasma specific fatty acids may exert differential effects on glucose-stimulated insulin secretion (GSIS), insulin sensitivity and clearance.Subjects and methods We examined the effect of oral ingestion, at regular intervals for 24 h, of an emulsion containing either predominantly monounsaturated (MUFA), polyunsaturated (PUFA) or saturated (SFA) fat or water (control) on GSIS, insulin sensitivity and insulin clearance in seven overweight or obese, non-diabetic humans. Four studies were conducted in each individual in random order, 4–6 weeks apart. Twenty-four hours after initiation of oral ingestion, subjects underwent a 2 h, 20 mmol/l hyperglycaemic clamp to assess GSIS, insulin sensitivity and insulin clearance.Results Following oral ingestion of any of the three fat emulsions over 24 h, plasma NEFAs were elevated by ∼1.5- to 2-fold over the basal level. Ingestion of any of the three fat emulsions resulted in reduction in insulin clearance, and SFA ingestion reduced insulin sensitivity. PUFA ingestion was associated with an absolute reduction in GSIS, whereas insulin secretion failed to compensate for insulin resistance in subjects who ingested SFA.Conclusions/interpretation Oral ingestion of fats with differing degrees of saturation resulted in different effects on insulin secretion and action. PUFA ingestion resulted in an absolute reduction in insulin secretion and SFA ingestion induced insulin resistance. Failure of insulin secretion to compensate for insulin resistance implies impaired beta cell function in the SFA study.Electronic Supplementary Material Supplementary material is available for this article at     

Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects

OBJECTIVES: The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN: . Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity. SETTING: University research laboratory. SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr). MAIN OUTCOME MEASURE: Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure. RESULTS: The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure. CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.     

Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus

The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. After MaxEPA treatment, there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids, while the n-6 fatty acid content decreased. The very low density lipoprotein (VLDL) triglyceride concentrations decreased significantly (by 22%) on MaxEPA treatment. However, these changes were not significantly different from those observed during the placebo period. The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear.     

Effects of hypocaloric dietary treatment enriched in oleic acid on LDL and HDL subclass distribution in mildly obese women.

OBJECTIVE: To study the effects of a carbohydrate-enriched (HiCarbo) or olive-oil-enriched (HiMUFA) hypocaloric diet on plasma lipoprotein levels and physical properties. DESIGN: A six-month follow-up dietary intervention study with a HiCarbo diet providing 60% of total calories as complex carbohydrates, 15% as proteins and 25% as fats [10% saturated (SFA); 7% monounsaturated (MUFA); 8% polyunsaturated fatty acids (PUFA)]; or a HiMUFA diet with 40% complex carbohydrates, 15% proteins and 45% fats (10% SFA; 27% MUFA; 8% PUFA). SUBJECTS: Twenty consecutive, mildly obese, normolipidemic premenopausal women (11 on HiCarbo and nine on HiMUFA diets) and 14 age- and sex-matched, lean controls. MEASUREMENTS: Body mass index (BMI), waist/hip ratio, plasma lipoproteins, apolipoprotein (apo) AI and B, LDL and HDL density distribution, and phospholipid fatty acid composition at baseline, and after 3 and 6 months on dietary treatment. RESULTS: Body weight progressively decreased during the first 3 months and then it stabilized during the following 3 months (-11% vs. baseline in both groups; P < 0.01). LDL-Cholesterol decreased significantly in both groups. HDL-Cholesterol increased significantly in the HiMUFA group, whereas a decreased level was observed in the HiCarbo group. At baseline the obese women had higher very low density lipoprotein (VLDL) and dense LDL-Cholesterol, and lower HDL2 cholesterol levels than the controls; these abnormalities persisted in the HiCarbo diet, whilst a significant decrease in the dense LDL associated with an increase in the HDL2 cholesterol was seen in the HiMUFA diet. HDL3 was not affected by either diet. The LDL/HDL-Cholesterol ratio was not affected by the HiCarbo diet, whilst it was significantly reduced after 6 months of HiMUFA diet as compared with baseline. Apo AI increased in the HiMUFA group, and decreased in the HiCarbo group. CONCLUSIONS: Both diets were effective in decreasing body weight. At steady weight conditions, only the HiMUFA diet improved LDL and HDL subclass distribution abnormalities present in mildly obese normolipidemic women.     

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

Aims/hypothesis  Previous studies have shown relationships between fatty acid ratios in adipose tissue triacylglycerol (TG), adipocyte size and measures of insulin sensitivity. We hypothesised that variations in adipose tissue de novo lipogenesis (DNL) in relation to adiposity might explain some of these observations. Methods  In a cross-sectional study, subcutaneous abdominal adipose tissue biopsies from 59 people were examined in relation to fasting and post-glucose insulin sensitivity. Adipocyte size, TG fatty acid composition and mRNA expression of lipogenic genes were determined. Results  We found strong positive relationships between adipose tissue TG content of the fatty acids myristic acid (14:0) and stearic acid (18:0) with insulin sensitivity (HOMA model) (p < 0.01 for each), and inverse relationships with adipocyte size (p < 0.01, p < 0.05, respectively). Variation in 18:0 content was the determinant of the adipose tissue TG 18:1 n-9/18:0 ratio, which correlated negatively with insulin sensitivity (p < 0.01), as observed previously. Adipose tissue 18:0 content correlated positively with the mRNA expression of lipogenic genes (e.g. FASN, p < 0.01). Lipogenic gene expression (a composite measure derived from principal components analysis) was inversely correlated with adipocyte cell size (p < 0.001). There was no relationship between dietary saturated fatty acid intake and adipose tissue 18:0 content. Conclusions/interpretation  Our data suggest a physiological mechanism whereby DNL is downregulated as adipocytes expand. Taken together with other data, they also suggest that hepatic and adipose tissue DNL are not regulated in parallel. We also confirm a strong relationship between small adipocytes and insulin sensitivity, which is independent of BMI. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Plasma and dietary vitamin E in relation to insulin secretion and sensitivity

Aim:  In the Insulin Resistance and Atherosclerosis Study (IRAS), we have previously shown a protective effect of plasma α-tocopherol concentration against diabetes incidence among persons not taking vitamin E supplements. The biologic mechanism for such a protective effect could involve improvement in either insulin sensitivity (S_I), insulin secretion or both. Thus, we examined vitamin E in relation to insulin secretion and S_I among persons not taking vitamin E supplements.
Methods:  This analysis included 457 adults aged 40–69 years without a previous diabetes diagnosis or vitamin E supplement use at baseline and seen at the 5-year follow-up examination. Baseline nutrient intake was estimated from a validated 1-year food frequency questionnaire; plasma levels of α-tocopherol were also assessed. At follow up, a frequently sampled intravenous glucose tolerance test determined S_I, acute insulin response to glucose (AIR), and the disposition index (DI) was calculated as the sum of the log-transformed AIR and S_I to reflect pancreatic compensation for insulin resistance.
Results:  In multivariable regression analyses, no relationship was observed for vitamin E intake and either S_I, AIR or DI. However, plasma α-tocopherol concentration was positively associated with log-transformed S_I (β= 0.27 ± 0.09, p < 0.01) and DI (β= 0.41 ± 0.14, p < 0.01), but not with log-transformed AIR.
Conclusions:  Plasma concentration of α-tocopherol may improve S_I and pancreatic compensation for insulin resistance, although it does not seem to be related to acute insulin response.     

Relationship between visceral fat,steroid hormones and insulin sensitivity in premenopausal obese women

Abstract: Objectives. The relationships between visceral fat distribution, steroid hormones and peripheral insulin sensitivity were studied. Setting. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona, Italy. Subjects. Nineteen fertile obese women were studied with ages ranging from 18 to 53 years and body mass indexes ranging from 27.3 to 48.4. Intervention. Body fat distribution was evaluated by waist-to-hip circumference ratio and by computed tomography. The insulin tolerance test was used to evaluate peripheral insulin sensitivity. Glucose, insulin and C-peptide were measured in fasting conditions and during glucose load; total and free plasma testosterone and urinary cortisol excretion were also determined. Results. Significant correlations emerged between visceral adipose tissue and fasting glucose, insulin, and C-peptide. but not between visceral adipose tissue and total testosterone, free testosterone or urinary cortisol excretion. A negative correlation emerged between visceral adipose tissue and insulin sensitivity (r = ?0.70; P < 0.01). No significant correlations were found between insulin sensitivity and age, body weight, body mass index, total adipose tissue, subcutaneous adipose tissue or waist-to-hip ratio. Total testosterone correlated with body weight, subcutaneous adipose tissue and total adipose tissue. Free testosterone and urinary cortisol excretion correlated positively with body weight, and negatively with age. No correlation was found between insulin sensitivity and total testosterone, free testosterone or urinary cortisol excretion. The correlation between visceral adipose tissue and insulin sensitivity remained significant even after adjusting for both age and the body mass index. Conclusions. Our study shows that visceral fat is more closely associated with aberrations of insulin sensitivity than with obesity itself. Total testosterone, free testosterone and urinary cortisol excretion in our subjects do not seem to be associated with such aberrations.     

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man

Summary The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70±7 vs. 52±7mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61±7; ASA, 65±6mol·kg^–1·min^–1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU·kg^–1·min^–1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103±4vs. 89±4mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 ±1.1 mmol/l) and hepatic glucose production (15±2 mol·kg^–1·min^–1) fell upon ASA treatment (8.6±0.7 mmol/l; 13±1 mol·kg^–1· min^–1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent. It is concluded that in healthy and Type 2 diabetic man, ASA impairs tissue sensitivity to the action of insulin. This effect is counterbalanced by an augmented plasma insulin response to glucose, which results from a reduced insulin clearance rate. In Type 2 diabetic patients, the reduction in hepatic glucose production may be responsible for the amelioration of hyperglycaemia following ASA treatment.     

Insulin secretion and insulin sensitivity in diabetic subgroups: studies in the prediabetic and diabetic state

Aims/hypothesis. To evaluate insulin sensitivity and insulin secretion in prediabetic and diabetic subjects with mutations in MODY1 (HNF-4α) and MODY3 (HNF-1α) genes, in subjects with GAD antibodies, latent autoimmune diabetes in adults and in subjects with the common form of Type II (non-insulin-dependent) diabetes mellitus. Methods. Insulin secretion was measured as the incremental 30-min insulin (I30) and insulin glucose ratio (I:G30) during OGTT whereas insulin sensitivity was measured as the insulin sensitivity index during OGTT in 131 carriers of MODY mutations [NGT = 38, IFG/IGT = 21, diabetes mellitus (DM) = 72], in 293 subjects with GADA (NGT = 47, IFG/IGT = 29, DM = 217) and in 2961 subjects with a family history of the common form of Type II diabetes but without MODY mutations or GADA (NGT = 1360, IFG/IGT = 857, DM = 744). A subgroup of the subjects underwent a euglycaemic clamp (n = 210) and intravenous glucose tolerance test (n = 337) for the estimation of insulin sensitivity and first-phase insulin secretion. Results. Non-diabetic subjects with MODY mutations had pronounced impaired insulin secretion (I30, I:G30) compared with the two other groups (p = 0.005). Normal or non-diabetic glucose tolerance was maintained by enhanced insulin sensitivity compared with the other two groups (p < 0.05 and p < 0.005). In contrast to patients with Type II diabetes and with adult latent autoimmune diabetes, MODY patients showed only a modest deterioration in insulin sensitivity at onset of diabetes. The 2-h glucose values inversely correlated with insulin sensitivity in subjects with GADA (r = –0.447, p < 0.001) and subjects from Type II diabetic families (r = –0.426, p < 0.001), whereas no such relation was observed in subjects with MODY mutations (r = 0.151, p = NS). There were no statistically significant differences in insulin secretion or insulin sensitivity between subjects with GADA or subjects with a family history of Type II diabetes, either at the NGT or the IFG/IGT stage. Conclusion/interpretation. Glucose-tolerant carriers of MODY mutations are characterised by a severe impairment in insulin secretion. Enhanced insulin sensitivity is the most likely explanation for the normal glucose tolerance. Whereas subjects with positive GADA or Type II diabetes have impaired insulin sensitivity with increasing glucose concentrations, MODY mutation carriers seem to be protected from the effect of glucose toxicity. [Diabetologia (2000) 43: 1476–1483] Received: 23 March 2000 and in revised form: 29 August 2000     

The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed Type II diabetes: the Insulin Resistance Atherosclerosis Study

Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r _s = –0.42) and intact proinsulin (r _s = –0.32) (p < 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r _s = 0.23) and inversely with the intact proinsulin:insulin ratio (r _s = –0.29, p < 0.001). Fasting glucose correlated positively with intact proinsulin (r _s = 0.34) and the intact proinsulin:insulin ratio (r _s = 0.24, p < 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p < 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066] Received: 25 February 1999 and in revised form: 12 April 1999     

Adiponectin in relation to insulin sensitivity and insulin secretion in the development of type 2 diabetes: a prospective study in 64-year-old women

Abstract. Fagerberg B, Kellis D, Bergström G, Behre CJ (Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden). Adiponectin in relation to insulin sensitivity and insulin secretion in the development of type 2 diabetes: a prospective study in 64‐year‐old women. J Intern Med 2011; 269 : 636–643. Objectives. To examine how serum adiponectin levels predict the incidence of type 2 diabetes, from different prediabetic states, in relation to insulin sensitivity and β‐cell function during 5.5 years of follow‐up. Methods. In a population‐based cohort of 64‐year‐old Caucasian women, we assessed glucose tolerance, insulin sensitivity as homeostasis model assessment, insulin secretion as acute insulin response, lifestyle factors and serum concentrations of adiponectin and high‐sensitivity C‐reactive protein. After 5.5 years of follow‐up, 167 women with normal glucose tolerance (NGT) and 174 with impaired glucose tolerance (IGT) at baseline were re‐examined and incidence of diabetes was assessed. Results. A total of 69 new cases of diabetes were detected during follow‐up. Diabetes incidence was independently predicted by low levels of serum adiponectin, insulin resistance and insulin secretion, cigarette smoking, impaired fasting glucose (IFG) and IGT at baseline. Serum adiponectin below 11.54 g L^?1 was associated with an odds ratio of 3.6 (95% confidence interval 1.4–8.6) for future type 2 diabetes. At baseline, a high serum adiponectin concentration correlated positively with high levels of insulin sensitivity and insulin secretion. Women with incident diabetes had lower serum adiponectin levels in the NGT, IFG and IGT groups at baseline compared to those who did not develop diabetes during follow‐up. Conclusions. Low adiponectin concentrations were associated with future diabetes independently of insulin secretion and sensitivity, as well as IGT, IFG, smoking and abdominal obesity.     

Different dietary fatty acids are associated with blood lipids in healthy South African men and women: The PURE study

Background

Preliminary data from the baseline Prospective Urban Rural Epidemiology (PURE) study in South Africa indicated a higher prevalence of dyslipidemia than previous South African studies. The intake of specific individual dietary fatty acids may affect blood lipids differently than sub-groups of fat (i.e. polyunsaturated fatty acids). We investigated the dietary intake of different individual fatty acids and their associations with blood lipids, in relation to urbanization and gender.

Methods

Cross-sectional data analysis within the PURE baseline study of healthy subjects (n = 1950, 35–70 years) from rural and urban areas. Dietary data were collected and blood lipid analysis performed.

Results

Intake of individual fatty acids was significantly higher in urban than rural dwellers. However, the intake of n-3 PUFAs was below recommendations in all groups. Total cholesterol and LDL were higher in females than in males, with no rural?urban differences. Intake of alpha-linolenic acid (ALA) was positively associated with total cholesterol (β = 0.143) and triglycerides (β = 0.256) in males. The risk for having elevated LDL also increased with increased intake of ALA (OR 1.49, 95% CI 1.04, 2.14) in males. In females, arachidonic acid and eicosapentaenoic acid (EPA) were positively associated with total cholesterol and arachidonic acid was also positively associated with LDL, whereas docosahexaenoic acid was negatively associated with total cholesterol and LDL.

Conclusions

These results suggest that specific individual dietary fatty acids may affect blood lipids in males differently than in females irrespective of rural or urban dwelling. The positive association between ALA and total cholesterol and triglycerides in males is a concern, because current advice aims to improve the dietary linoleic acid to ALA ratio by increasing ALA intake.     

Glucose intolerance is predicted by low insulin secretion and high glucagon secretion: outcome of a prospective study in postmenopausal Caucasian women

Aims/hypothesis. To study the pathophysiological importance of changes in insulin sensitivity and islet function over time for alterations in glucose tolerance in a randomly selected large group of non-diabetic women aged 57–59 years over a 3-year period.¶Methods. At baseline and at the 3-year follow-up, glucose tolerance (WHO 75 g oral glucose), insulin sensitivity (euglycaemic, hyperinsulinaemic clamp) and insulin and glucagon secretion (2 to 5-min responses to 5 g i. v. arginine at fasting, 14 and > 25 mmol/l glucose) were measured.¶Results. At baseline, women with impaired glucose tolerance (IGT, n = 28) had lower insulin sensitivity (p = 0.048) than normal women (NGT, n = 58). The arginine-induced insulin responses (AIR) were inversely associated with insulin sensitivity (r≥– 0.55, p < 0.001). When related to the 3-year follow-up, the baseline product of AIR at 14 mmol/l glucose times insulin sensitivity, insulin effect index (IE) (r = – 0.40, p < 0.001) and the arginine-induced glucagon response at 14 mmol/l glucose (AGR, r = 0.28, p = 0.009) both correlated with follow-up 2-h glucose. In a multiple regression model, baseline 2-h glucose, insulin effect index and arginine-induced glucagon response independently predicted 2-h glucose at follow-up (total r = 0.668, p < 0.001). Furthermore, Δinsulin sensitivity (i. e. follow-up minus baseline) correlated with Δinsulin secretion (r = – 0.30, p = 0.006), whereas Δglucagon secretion correlated with Δ2-h glucose (r = 0.30, p = 0.006) over the 3 years. In a multiple regression, alterations in 2-h glucose over the 3 years were independently determined by changes in fasting insulin and glucagon secretion (r = 0.424, p < 0.001).¶Conclusion/interpretation. Low insulin secretion, when judged in relation to insulin sensitivity, and high glucagon secretion, determine glucose tolerance over time in the individual subject. These processes are therefore potential targets for prevention of deterioration in glucose tolerance. [Diabetologia (2000) 43: 194–202]     

Erythrocyte membrane n-3 fatty acid levels and carotid atherosclerosis in Chinese men and women

Objective

Prospective studies have supported the beneficial effects of n-3 fatty acid consumption on cardiac deaths, but limited data focused on atherosclerosis. We investigated the associations between n-3 fatty acids in erythrocytes and atherosclerosis in middle-aged and older Chinese.

Methods

847 subjects (285 men and 562 women), aged 40–65 years, from Guangzhou, China were included in this community-based cross-sectional study between December 2005 and January 2008. The levels of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. Carotid ultrasound examination was conducted to obtain intima–media thickness of the common carotid artery and the carotid bifurcation. Dietary data and other covariates were collected using interviewer-administered questionnaires.

Results

After adjustment for age, sex, and other confounders, negative dose–response associations between the contents of individual n-3 polyunsaturated fatty acids in the erythrocyte membrane and the prevalence of carotid artery wall thickening and plaque were observed. A comparison in the highest and lowest tertiles gave odds ratios (95% confidence interval) for thickening in the walls of the common carotid artery of 0.58 (0. 34–0.97; P-trend = 0. 037) for DHA, and 0.39 (0.23–0.67; P-trend < 0.001) for ALA. However, EPA was not significantly associated with carotid atherosclerosis. Similar results were found for thickening at the carotid bifurcation and the occurrence of carotid artery plaque.

Conclusions

Higher levels of DHA and ALA in the erythrocyte membrane were significantly associated with a lower burden of subclinical atherosclerosis.