Home blood sampling for plasma glucose assay in control of diabetes.

Estimation of plasma glucose in home blood samples is needed to improve diabetic control. Sufficiently precise measurements on capillary blood were obtained by (a) storing Reflotest glucose-oxidase strips in a desiccant container before reading and (b) collecting blood samples into a simple vacuum bottle containing potassium fluoride (assay of sodium content indicating volume of plasma collected). The precision of the methods (+/- 1 SD) was +/-0.35 mmol/1 (+/-6.3 mg/100 ml). Clinical reliability was assessed by measuring the basal plasma glucose concentration at home on different mornings in patients with maturity-onset diabetes, the day-to-day variation (+/- 1 SD) being +/-0.73 and +/-0.92 mmol/1 (+/-13.2 and +/-16.6 mg/100 ml) respectively. The mean basal plasma glucose concentration in all 84 patients with maturity-onset diabetes from three general practices was 8 mmol/1 (144 mg/100 ml), 44 of the values exceeding 6 mmol/1 (108 mg/100 ml). Improving control by monitoring the basal plasma glucose concentration in maturity-onset diabetes might help to prevent diabetic complications.     

Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome

Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m²) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.     

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.     

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites.

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.     

Studies on lipogenesis in vivo. Lipogenesis during extended periods of re-feeding after starvation

1. Lipogenesis was studied in mice re-fed for up to 21 days after starvation. At appropriate times [U-(14)]glucose was given by stomach tube and incorporation of (14)C into various lipid fractions measured. 2. In mice starved for 48hr. and then re-fed for 4 days with a diet containing 1% of corn oil, incorporation of (14)C from [U-(14)C]glucose into liver fatty acids and cholesterol was respectively threefold and eightfold higher than in controls fed ad libitum. The percentages by weight of fatty acids and cholesterol in the liver also increased and reached peaks after 7 days. Both the radioactivity and weights of the fractions returned to control values after 10-14 days' re-feeding. These changes could be diminished by re-feeding the mice with a diet containing 20% of corn oil. Incorporation of (14)C from [U-(14)C]glucose into extrahepatic fatty acids (excluding those of the epididymal fat pads) was not elevated during re-feeding with a diet containing either 1% or 20% of corn oil. However, incorporation of (14)C from [U-(14)C]glucose into the fatty acids of the epididymal fat pads was increased in mice re-fed with either diet, as compared with non-starved controls. 3. Lipogenesis was also studied in mice alternately fed and starved. Mice given a diet containing 1% of corn oil for 6hr./day for 4 weeks lost weight initially and never attained the weight or carcass fat content of controls fed ad libitum. Incorporation of (14)C from dietary [U-(14)C]-glucose into the fatty acids of the epididymal fat pads was elevated threefold in the mice allowed limited access to food, although the incorporation into the remainder of the extrahepatic fatty acids was not different from that found for controls. Mice given a diet containing 20% of corn oil for 6hr./day adapted to the limited feeding regimen quicker and in 4 weeks did attain the weight and carcass fat content of controls. Incorporation of (14)C from [U-(14)C]glucose into the fatty acids of the epididymal fat pads and the remainder of the extrahepatic fatty acids was respectively fivefold and threefold higher than in controls fed ad libitum. 4. The elevation in liver lipogenesis during re-feeding was greatest on a diet containing 1% of corn oil, whereas in extrahepatic tissues the increase in lipogenesis was greater when the mice were re-fed or were allowed limited access to a diet containing 20% of corn oil. These results suggest that the causes of the increased rate of incorporation of (14)C from [U-(14)C]glucose into fatty acids during re-feeding may be different in liver from that in extrahepatic tissues.     

Manipulation of dietary carbohydrate and muscle glycogen affects glucose uptake during exercise when fat oxidation is impaired by beta-adrenergic blockade

We have recently reported that, during moderate intensity exercise, low muscle glycogen concentration and utilization caused by a high-fat diet is associated with a marked increase in fat oxidation with no effect on plasma glucose uptake (R(d) glucose). It is our hypothesis that this increase in fat oxidation compensates for low muscle glycogen, thus preventing an increase in R(d) glucose. Therefore, the purpose of this study was to determine whether low muscle glycogen availability increases R(d) glucose under conditions of impaired fat oxidation. Six cyclists exercised at 50% peak O(2) consumption (Vo(2 peak)) for 1 h after 2 days on either a high-fat (HF, 60% fat, 24% carbohydrate) or control (CON, 22% fat, 65% carbohydrate) diet to manipulate muscle glycogen to low and normal levels, respectively. Two hours before the start of exercise, subjects ingested 80 mg of propanolol (betaB), a nonselective beta-adrenergic receptor blocker, to impair fat oxidation during exercise. HF significantly decreased calculated muscle glycogen oxidation (P < 0.05), and this decrease was partly compensated for by an increase in fat oxidation (P < 0.05), accompanied by an increase in whole body lipolysis (P < 0.05), despite the presence of betaB. Although HF increased fat oxidation, plasma glucose appearance rate, R(d) glucose, and glucose clearance rate were also significantly increased by 13, 15, and 26%, respectively (all P < 0.05). In conclusion, when lipolysis and fat oxidation are impaired, in this case by betaB, fat oxidation cannot completely compensate for a reduction in muscle glycogen utilization, and consequently plasma glucose turnover increases. These findings suggest that there is a hierarchy of substrate compensation for reduced muscle glycogen availability after a high-fat, low-carbohydrate diet, with fat being the primary and plasma glucose the secondary compensatory substrate. This apparent hierarchy likely serves to protect against hypoglycemia when endogenous glucose availability is low.     

Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile

Male Yucatan swine were allocated to four groups (n = 5-6 pigs per group): low fat (3%) fed control, high fat/2% cholesterol (CH) fed (HF), high fat/CH fed with alloxan-induced diabetes (DF) and DF pigs that were treated with atorvastatin (80 mg/day; DF+A). Pigs were fed two meals per day and daily insulin injections were used in diabetic pigs to maintain plasma glucose between 250 and 350 mg/dl. Diabetic dyslipidemic (DF) pigs exhibited greater coronary atherosclerosis and increased collagen deposition in internal mammary artery compared with normoglycemic hyperlipidemic pigs. Although total and LDL CH concentrations did not differ, triglyceride (TG) were increased in DF pigs and FPLC analysis indicated that the LDL/HDL CH ratio was significantly increased in DF compared with HF pigs. The LDL fraction of DF pigs contained larger, lipid enriched particles resembling IDL. Consumption of the high fat/CH diet caused a moderate increase in the percentage of 14:0 fatty acids in plasma lipids and this was compensated by small-moderate declines in several unsaturated fatty acids. There was a significant increase in phospholipid arachidonic acid in DF compared with HF pigs. Atorvastatin protected diabetic pigs from atherosclerosis and decreased total and VLDL TG, but exerted minimal effects on the FPLC lipoprotein and plasma fatty acid profiles and plasma concentrations of total and LDL CH, vitamin A, vitamin E, and lysophosphatidylcholine. Across all groups the plasma CH concentration was positively correlated with hepatic CH concentration. These findings suggest that atorvastatin's protection against coronary artery atherosclerosis in diabetes may involve effects on plasma VLDL TG concentration. Lack of major effects on other lipid parameters, including the LDL/HDL ratio, suggests that atorvastatin may have yet other anti-atherogenic effects, possibly directly in the vessel wall.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

A forage-only diet alters the metabolic response of horses in training

Most athletic horses are fed a high-starch diet despite the risk of health problems. Replacing starch concentrate with high-energy forage would alleviate these health problems, but could result in a shift in major substrates for muscle energy supply from glucose to short-chain fatty acids (SCFA) due to more hindgut fermentation of fibre. Dietary fat inclusion has previously been shown to promote aerobic energy supply during exercise, but the contribution of SCFA to exercise metabolism has received little attention. This study compared metabolic response with exercise and lactate threshold (V_La4) in horses fed a forage-only diet (F) and a more traditional high-starch, low-energy forage diet (forage–concentrate diet - FC). The hypothesis was that diet F would increase plasma acetate concentration and increase V_La4 compared with diet FC. Six Standardbred geldings in race training were used in a 29-day change-over experiment. Plasma acetate, non-esterified fatty acids (NEFA), lactate, glucose and insulin concentrations and venous pH were measured in samples collected before, during and after a treadmill exercise test (ET, day 25) and muscle glycogen concentrations before and after ET. Plasma acetate concentration was higher before and after exercise in horses on diet F compared with diet FC, and there was a tendency (P = 0.09) for increased V_La4 on diet F. Venous pH and plasma glucose concentrations during exercise were higher in horses on diet F than diet FC, as was plasma NEFA on the day after ET. Plasma insulin and muscle glycogen concentrations were lower for diet F, but glycogen utilisation was similar for the two diets. The results show that a high-energy, forage-only diet alters the metabolic response to exercise and, with the exception of lowered glycogen stores, appears to have positive rather than negative effects on performance traits.     

In vivo model for dyslipidemia with diabetes mellitus in hamster

Due to similarities in lipid metabolism to those in humans, hamster is considered as a good model for the study of regulatory mechanisms of plasma lipoproteins in response to cholesterol or fatty acid-enriched diet. This model of hyperlipidemia has been modified to produce dyslipidedmia with diabetes complexities by feeding with high fat diet added with 9% (w/w) fructose. Feeding this diet to hamster for 10 days markedly increases plasma levels of triglyceride, cholesterol, fatty acids followed by a significant increase in glycerol, beta lipoproteins, high density lipoprotein, glucose and glycosylated proteins. This model is being used for research and development of lipid lowering drugs with hypoglycemic activity in collaboration with Novo Nordisk, Denmark. The modified high fat diet formulation has now been prepared (Research diet D.99122211) and supplied by Research Diets Inc, Burnswick USA.     

Insulin secretion after dietary supplementation with conjugated linoleic acids and n-3 polyunsaturated fatty acids in normal and insulin-resistant mice

Conjugated linoleic acids (CLAs) and n-3 polyunsaturated fatty acids (PUFAs) improve insulin sensitivity in insulin-resistant rodents. However, the effects of these fatty acids on insulin secretion are not known but are of importance to completely understand their influence on glucose homeostasis. We therefore examined islet function after dietary supplementation consisting of 1% CLAs in combination with 1% n-3 enriched PUFAs for 12 wk to mice on a normal diet and to insulin-resistant mice fed a high-fat diet (58% fat). In the mice fed a normal diet, CLA/PUFA supplementation resulted in insulin resistance associated with low plasma adiponectin levels and low body fat content. Intravenous and oral glucose tolerance tests revealed a marked increase in insulin secretion, which nevertheless was insufficient to counteract the insulin resistance, resulting in glucose intolerance. In freshly isolated islets from mice fed the normal diet, both basal and glucose-stimulated insulin secretion were adaptively augmented by CLA/PUFA, and at a high glucose concentration this was accompanied by elevated glucose oxidation. In contrast, in high-fat-fed mice, CLA/PUFA did not significantly affect insulin secretion, insulin resistance, or glucose tolerance. It is concluded that dietary supplementation of CLA/PUFA in mice fed the normal diet augments insulin secretion, partly because of increased islet glucose oxidation, but that this augmentation is insufficient to counterbalance the induction of insulin resistance, resulting in glucose intolerance. Furthermore, the high-fat diet partly prevents the deleterious effects of CLA/PUFA, but this dietary supplementation was not able to counteract high-fat-diet-induced insulin resistance.     

The signal transduction pathway of PKC/NF-κB/c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats

Background

Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin.

Methods

In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accordance with dietary guidelines during two consecutive 3-month periods. Outcome variables included changes in weight, waist circumference, serum lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food records.

Results

Study participants had on average a diabetes duration of 9 years, a mean HbA1c of 6,6% units by Mono-S standard and were usually treated with metformin alone (3 subjects) or metformin in combination with a sulfonylurea (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted in lower mean values of HbA1c (-0.4% units, p = 0.01), triacylglycerol (-0.4 mmol/L, p = 0.003), diastolic blood pressure (-4 mmHg, p = 0.03), weight (-3 kg, p = 0.01), BMI (-1 kg/m², p = 0.04) and waist circumference (-4 cm, p = 0.02), and higher mean values of high density lipoprotein cholesterol (+0.08 mmol/L, p = 0.03). The Paleolithic diet was mainly lower in cereals and dairy products, and higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet. Further, the Paleolithic diet was lower in total energy, energy density, carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and higher in unsaturated fatty acids, dietary cholesterol and several vitamins. Dietary GI was slightly lower in the Paleolithic diet (GI = 50) than in the Diabetic diet (GI = 55).

Conclusion

Over a 3-month study period, a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT00435240.     

Effect of non-digestible gluco-oligosaccharides on glucose sensitivity in high fat diet fed mice

Non digestible dietary carbohydrates have been reported to modify lipaemia and post-prandial glycaemia and insulinaemia. The aim of this study was to investigate the effect of a non-digestible gluco-oligosaccharides (GOS) diet on glucose, insulin, triglycerides and free fatty acid blood levels and glucose sensitivity in high fat diet fed mice (a high fat diet composed of 45% fat, 35% carbohydrate and 20% protein). Female C57B16/J mice were divided into two groups fed a high fat diet (HF) for 20 weeks supplemented or not with 1.5 g/kg/day of GOS (HF-GOS). The GOS supplementation did not change body weight nor fat pad mass, nor any of the blood parameters measured (glucose, insulin, leptin, triglycerides, and free fatty acids). However, mice which received the GOS supplemented diet showed an increased glucose utilization after a 1 g/kg load of glucose compared with the mice fed the high fat diet alone. Our results suggest a role for non-digestible GOS in the regulation of carbohydrate metabolism.     

Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids.

Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.     

Adipokines and adipocyte function in Clock mutant mice that retain melatonin rhythmicity

Clock(δ19)+MEL mutant mice, which retain melatonin rhythmicity, but lack peripheral tissue rhythmicity have impaired glucose tolerance, but reduced plasma free fatty acids, increased plasma adiponectin, and improved insulin sensitivity. Here, we report their response to a high-fat diet and adipocyte rhythmicity and function. The diet increased epigonadal fat weight similarly (twofold) in both wild-type and Clock(δ19)+MEL mice. The Clock(δ19) mutation abolished rhythmicity of Per2, Rev erbα and peroxisome proliferator-activated receptor-γ (Pparγ ) mRNA in epigonadal fat, but not Bmal1 mRNA, and reduced Rev erbα mRNA by 59 and 70% compared to the wild-type mice on the control and high-fat diets, respectively. The mutants had increased Adipoq mRNA expression in epigonadal fat (22%; P < 0.05) on a control diet, but showed no further change on a high-fat diet, and no change in Lep, Nampt or Retn mRNA on either diet. The Clock(δ19) mutation abolished rhythmicity of genes in epigonadal fat that contribute to plasma free fatty acids for mice on both diets, and increased Lipe mRNA expression in those on the high-fat diet. The persistent melatonin rhythm and reduced plasma free fatty acids in Clock(δ19)+MEL mutants may contribute to their enhanced insulin sensitivity, ameliorate the extent of impaired glucose homeostasis, and protect against the adverse effects of a high-fat diet.     

Role of fatty acid composition in the development of metabolic disorders in sucrose-induced obese rats

Fatty acids have been shown to be involved in the development of insulin resistance associated with obesity. We used sucrose loading in rats to analyze changes in fatty acid composition in the progression of obesity and the related metabolic disorder. Although rats fed a sucrose diet for 4 weeks had body weights similar to those of control animals, their visceral fat pads were significantly larger, and serum triglyceride levels were higher; however, neither plasma glucose nor insulin levels were significantly higher. After 20 weeks of sucrose loading, body weight and visceral and subcutaneous fat pads had increased significantly compared with those in control rats. Moreover, plasma glucose, insulin, and triglyceride levels were significantly higher. An analysis of individual fatty acid components in the blood and peripheral tissues demonstrated phase- and tissue-dependent changes. After 20 weeks of sucrose loading, palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9), the major components of monounsaturated fatty acid, showed a ubiquitous increase in plasma and all tissues analyzed. In contrast, linoleic acid (18:2 n-6) and arachidonic acid (20:4 n-6), the major components of polyunsaturated fatty acid in the n-6 family, decreased in plasma and all tissues analyzed. After 4 weeks of sucrose loading, these changes in fatty acid composition were observed only in the liver and plasma and not in fat and muscle. This led us to conclude that elevation of plasma glucose and insulin develop at the late phase of sucrose-induced obesity, when changes in fatty acid composition appear in fat and muscle. Furthermore, changes in fatty acid composition in liver seen after 4 weeks of sucrose loading, when increases in neither plasma glucose nor insulin were detected, suggest that liver may be the initial site of fatty acid imbalance and that aberrations in hepatic fatty acid composition may lead to fatty acid imbalances in other tissues.     

Influence of dietary fatty acids composition, level of dietary fat and feeding period on some parameters of androgen metabolism in male rats

The aim of the present study was to determine the effect of the composition of dietary fatty acids, the duration of feeding period and dietary fat level on androgen metabolism in male rats. One hundred and twelve Wistar rats were divided into 18 groups which were fed three diets containing different types of fat (rapeseed [R], palm [P] and fish [F] oil) at either normal fat level (w/w; 5%) or high fat level (20%) during one, three or six weeks. Blood plasma level of androgen (testosterone+dihydrotestosterone) and testicular activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were investigated. In addition, androgen content in cytosol of the heart, the target organ, was measured. Androgen concentration in both blood plasma and heart cytosol extracts was measured by radioimmunoassay. The activity of 17Beta-HSD was expressed as a conversion of [3H]androstendione to [3H]testosterone in soluble fraction of gonadal homogenates. Plasma androgen concentration was influenced by a type of dietary fat (p<0.05). The highest plasma level of androgen was observed in animals fed R diets rich in unsaturated fatty acids. Significantly lower androgen concentration was demonstrated in rats fed P diets rich in saturated fatty acids. Only the feeding period factor significantly influenced androgen content in cytosol fraction of heart muscle cells (p<0.01). A positive correlation was found between plasma androgen concentration in plasma and cytosol fraction of the heart muscle cells (r=0.63, p<0.001). The feeding period (p<0.001) and dietary fat type (p<0.05) significantly affected the activity of 17beta-HSD. The least 17beta-HSD activity was observed in animals consuming the P-20% diet for six weeks. In summary, dietary fat type and feeding period, but not fat level, significantly affected both testosterone production and testosterone uptake by the target organ in male rats. It was found that a rapeseed diet rich in unsaturated fatty acids stimulated the testicular function in rats.     

Low-Carbohydrate Diet and Type 2 Diabetes Risk in Japanese Men and Women: The Japan Public Health Center-Based Prospective Study

ObjectiveEvidence is sparse and contradictory regarding the association between low-carbohydrate diet score and type 2 diabetes risk, and no prospective study examined the association among Asians, who consume greater amount of carbohydrate. We prospectively investigated the association of low-carbohydrate diet score with type 2 diabetes risk.MethodsParticipants were 27,799 men and 36,875 women aged 45–75 years who participated in the second survey of the Japan Public Health Center-Based Prospective Study and who had no history of diabetes. Dietary intake was ascertained by using a validated food-frequency questionnaire, and low-carbohydrate diet score was calculated from total carbohydrate, fat, and protein intake. The scores for high animal protein and fat or for high plant protein and fat were also calculated. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over 5-year were estimated by using logistic regression.ResultsDuring the 5-year period, 1191 new cases of type 2 diabetes were self-reported. Low-carbohydrate diet score for high total protein and fat was significantly associated with a decreased risk of type 2 diabetes in women (P for trend <0.001); the multivariable-adjusted odds ratio of type 2 diabetes for the highest quintile of the score were 0.63 (95% confidence interval 0.46–0.84), compared with those for the lowest quintile. Additional adjustment for dietary glycemic load attenuated the association (odds ratio 0.75, 95% confidence interval 0.45–1.25). When the score separated for animal and for plant protein and fat, the score for high animal protein and fat was inversely associated with type 2 diabetes in women, whereas the score for high plant protein and fat was not associated in both men and women.DiscussionLow-carbohydrate diet was associated with decreased risk of type 2 diabetes in Japanese women and this association may be partly attributable to high intake of white rice. The association for animal-based and plant-based low-carbohydrate diet warrants further investigation.     

Influence of dietary fat on the concentration of long-chain unsaturated fatty acid families in rat tissues

The relative concentration of long-chain unsaturated fatty acids (chain length C(20) and greater) of the (n - 6), (n - 7), and (n - 9) families in the cholesteryl esters and phospholipids of rat adrenals, liver, heart, and plasma lipoproteins was measured after the feeding of hydrogenated fat, milk fat, beef tallow, corn oil, and fat-free diets. Barely optimal levels of dietary linoleate were found to result in the same order of concentration of the (n - 6) series of fatty acids as was obtained with excess dietary linoleate. The linoleate-poor or deficient diets-hydrogenated fat and fat-free diets-gave almost identical levels and trends with respect to the concentration of the (n - 9) and (n - 7) series of acids.With these two diets, the concentrations of the total (n - 9) long-chain acids were several times greater than the amounts obtained by feeding either the linoleate-rich diet or the barely linoleate-adequate diets. It is concluded from the results that the linoleate-deficient nature of the hydrogenated fat, rather than its high content of trans acids, would explain the high tendency of this fat to induce the accumulation of long-chain (n - 9) fatty acids in the cholesteryl esters and phospholipids of the tissues studied.     

The lipid composition of milk from mice fed high or low fat diets.

Total fatty acids and the proportions of methyl esters of individual fatty acids were measured in mouse milk. Pregnant mice were fed either a high fat (HF) diet or a low fat (LF) diet from 14 days of gestation. After parturition, each dam was milked once a day for a period of 18 days. The mean total fatty acid concentration over the entire study period was 110 mg/g of milk (approximately 11.7% fat as triglyceride) for both dietary treatment groups. During days 2 to 6 postpartum, the mean total fatty acid concentration for dams fed HF diet was lower than for the LF group. Although the concentration of total fatty acids of mouse milk was not affected by the level of dietary fat fed to the dam, several variations in the proportions of individual fatty acids were observed.