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Biomedical subjects

M Axelsen

Publications and source records attributed to M Axelsen.

17 recordsLinked to original sources
PubMed2006

Postprandial interstitial insulin concentrations in type 2 diabetes relatives.

BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.

Adipose Tissue↗
PubMed2004

Early alterations in the postprandial VLDL1 apoB-100 and apoB-48 metabolism in men with strong heredity for type 2 diabetes.

OBJECTIVES: To study the postprandial triglyceride-rich lipoprotein (TRL) metabolism, specifically the concentrations of very low-density lipoproteins (VLDL); from intestine (apoB-48) and liver (apoB-100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS AND SETTINGS: Sixteen healthy men with at least two first-degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8-h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7-day diet registration and computed tomography. RESULTS: The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB-48, P = 0.04 and 21% higher for VLDL1 apoB-100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low-density lipoprotein (LDL) size in both relatives (rs = -0.60, P = 0.03) and controls (rs = -0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB-48 and apoB-100 particles in the other fractions (plasma, chylomicron or VLDL2). CONCLUSION: Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin-resistant men.

Adult↗
PubMed2004

Attitudes and barriers to dietary advice aimed at reducing risk of type 2 diabetes in first-degree relatives of patients with type 2 diabetes.

OBJECTIVE: To evaluate the attitudes to and adoption of dietary advice in nondiabetic first-degree relatives of patients with type 2 diabetes and to examine barriers to adherence. DESIGN: One-year controlled intervention study, where treatment group (n=73) received lifestyle education. Attitudes towards dietary advice, change in dietary habits and importance of potential barriers to adherence were evaluated by questionnaires. Nondiabetic relatives (25-55 years; males and females) of individuals with type 2 diabetes were recruited. Education was based on current nutrition recommendations and aimed at improving dietary fat quality, increasing intake of fruit and vegetables, with additional advice to reduce dietary glycaemic index (GI). MAIN OUTCOME MEASURES: Attitudes and importance of barriers were classified by the intervened subjects into four categories ranging from 'No problem' to 'Yes, definitely a problem'. Dietary adherence was monitored by food frequency questionnaire at baseline and after 1 year. RESULTS: Participants were generally in favour of advice aimed at improving dietary fat quality. Attitudes towards advice to reduce GI varied widely. Food selection changed in accordance with predefined dietary goals. 'Forgetfulness', 'low availability in lunch restaurant' and 'lack of ideas for cooking' were barriers to adherence. CONCLUSIONS: Dietary advice aimed at reducing risk of type 2 diabetes was generally positively received and adopted in subjects with heredity for the disease. The most prevalent barriers reported are potentially modifiable.

Adult↗
PubMed2001

Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy.

OBJECTIVE: Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety. RESEARCH DESIGN AND METHODS: This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin. RESULTS: The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049). CONCLUSIONS: Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Adolescent↗
PubMed2000

Dietary fibre, lente carbohydrates and the insulin-resistant diseases.

Several epidemiological studies link consumption of fibre-rich foods to a reduced risk of type 2 diabetes and CHD. The 'fibre hypothesis' suggested that this was a direct effect of fibre. However, fibre-rich foods contain different types of fibre as well as other potentially beneficial compounds, and many foods naturally high in fibre have low glycaemic and insulinaemic indices, possibly due to food form. The question therefore emerges as to the effect of isolated fibre per se on insulin sensitivity, lipids and other risk factors associated with the metabolic syndrome. Many beneficial effects are seen with pharmacological doses of isolated viscous soluble fibre, including improved insulin sensitivity, decreased LDL-cholesterol levels and decreased clotting factors. Similar effects are seen with low glycaemic-index foods. In contrast, insoluble non-viscous cereal fibre is not seen to act directly on risk factors when taken in refined foods such as in milled flour. Since cereal fibre, the major type of fibre in western diets, does not directly act on the risk factors for the metabolic syndrome, the question remains as to possible mechanisms. Until now, fibre and the nature and processing of the starch and particle size have been seen as the main determinants of the metabolic response to starchy foods. However, fibre-rich foods also have an increased protein-to-carbohydrate ratio. Hence we suggest that the protective effect of fibre may also be due to increased vegetable protein content, which may act directly to reduce clotting factors and oxidized LDL-cholesterol levels.

Adult↗
PubMed2000

Suppression of nocturnal fatty acid concentrations by bedtime carbohydrate supplement in type 2 diabetes: effects on insulin sensitivity, lipids, and glycemic control.

BACKGROUND: Bedtime ingestion of slow-release carbohydrates leads to sustained nocturnal fatty acid suppression and improved glucose tolerance in type 2 diabetic patients. OBJECTIVE: This study assessed the effects of 2 different doses of bedtime carbohydrate supplement (BCS) on morning glycemic control and glycated hemoglobin (Hb A(1c)) in type 2 diabetic patients. In addition, the effects of the high-dose BCS on insulin sensitivity and postprandial glucose and triacylglycerol concentrations were assessed. DESIGN: Two BCS doses were studied separately in 7-wk randomized, placebo-controlled, double-blind studies with either a parallel (low-dose BCS; n = 24 patients) or crossover (high-dose BCS; n = 14 patients) design. The effects of the low and high doses (0.30 and 0.55 g uncooked cornstarch/kg body wt, respectively) were compared with those of a starch-free placebo. RESULTS: Compared with the starch-free placebo, the high-dose BCS ( approximately 45 g) produced enhanced nocturnal glucose (P < 0.01) and insulin (P < 0.01) concentrations as well as a 32% suppression of fatty acid concentrations (P < 0.01). Moreover, glucose tolerance (P < 0.05) and C-peptide response (P < 0.05) improved after breakfast the next morning. The low-dose BCS ( approximately 25 g) improved fasting blood glucose concentrations (P < 0.05). However, there were no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or Hb A(1c) after 7 wk. CONCLUSION: Nocturnal fatty acid suppression by BCS improved fasting and postprandial blood glucose concentrations in type 2 diabetic patients the next morning. In contrast, no improvements in insulin sensitivity, postprandial triacylglycerol concentrations, or long-term glycemic control assessed by Hb A(1c) were seen after BCS supplementation.

Blood Glucose↗
PubMed2000

Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease.

Viscous fibres such as guar, glucomannans, pectins, oat betaglucan and psyllium continue to be seen as hypocholesterolaemic. Nevertheless, in large cohort studies, ironically it is the insoluble cereal fibre that has been demonstrated to relate negatively to cardiovascular disease and diabetes, despite an absence of effect on fasting lipids or postprandial glycaemia. In general, resistant or nonabsorbable starch is lipid neutral, whereas some nonabsorbable sugars or oligosaccharides may raise serum cholesterol, possibly through providing more acetate after colonic fermentation by colonic microflora. On the other hand, fructo-oligosaccharides appear to reduce serum triglycerides for reasons that are not entirely clear. Of possibly greater recent interest have been the carbohydrates that are not so much resistant to absorption, but rather are slowly absorbed. They possess some of the features of dietary fibre in providing a substrate for colonic bacterial fermentation. In the small intestine, however, they form lente or sustained release carbohydrate. In the form of low glycaemic index foods, lente carbohydrate consumption has been shown to relate to improved blood lipid profiles in hyperlipidaemic individuals and improved glycaemic control in diabetes. In larger cohort studies, low glycaemic index foods or low glycaemic load diets have been associated with higher HDL-cholesterol levels and reduced incidence of diabetes and cardiovascular disease.

Blood Glucose↗
PubMed1999

Insulin signaling and action in fat cells: associations with insulin resistance and type 2 diabetes.

Adipose tissue only accounts for a relatively small proportion (< 10%) of the peripheral glucose utilization in response to insulin. However, the fat cells may still play an important role in insulin resistance and Syndrome X through, for instance, its endocrine functions (production of leptin, TNF alpha, PAI-1, etc.) and involvement in lipid metabolism (FFA release and hydrolysis of triglycerides). The fat cells are also highly sensitive to insulin and may thus be used to elucidate molecular mechanisms for insulin resistance in man. Examinations of the intracellular signaling mechanisms for insulin in fat cells from individuals with Type 2 diabetes revealed markedly lower insulin-stimulated PI3-kinase activity. This was due to a pronounced reduction in the cellular expression of the docking protein, IRS 1, whereas expression of IRS 2 was normal. However, IRS 2-associated PI3-kinase activity was only approximately one-third of that found to be associated with IRS 1 in normal cells. Downstream activation and serine phosphorylation of PKB/Akt by insulin were also markedly reduced in Type 2 diabetes. Furthermore, the dose-response curve for this effect of insulin was similar to that for glucose transport in both normal and Type 2 diabetic cells. Thus, these data show that both PI3-kinase and PKB activation by insulin are markedly reduced in Type 2 diabetes. We also examined whether an attenuated activation of PI3-kinase by insulin can be seen in non-diabetic insulin-resistant states. Approximately 30% of healthy subjects with at least two first-degree relatives with Type 2 diabetes exhibited perturbations in IRS-1 expression and signaling. These individuals were characterized by insulin resistance as well as other markers of Syndrome X. Thus, impaired IRS-1 expression and downstream signaling events in fat cells in response to insulin are associated with insulin resistance and Syndrome X.

Adipocytes↗
PubMed1999

Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes.

BACKGROUND: Impaired ability to eliminate lipids in the postprandial state is an atherogenic trait associated with insulin resistance. OBJECTIVE: To assess insulin sensitivity and postprandial triglyceride metabolism in prediabetic persons. DESIGN: Cross-sectional study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: 13 healthy, normotriglyceridemic men with two first-degree relatives with type 2 diabetes and 13 carefully matched controls without known diabetes heredity. MEASUREMENTS: Oral glucose tolerance test, insulin sensitivity (euglycemic clamp technique), and fasting and postprandial triglyceride levels after a mixed meal. RESULTS: Relatives of persons with type 2 diabetes were insulin resistant but had normal glucose tolerance. They exhibited postprandial hypertriglyceridemia; the 6-hour triglyceride incremental area under the curve was 50% higher than that of the control group (P = 0.037). CONCLUSIONS: These healthy male first-degree relatives of patients with type 2 diabetes are insulin resistant and exhibit postprandial lipid intolerance despite having normal fasting triglyceride levels. These characteristics, which occur in the absence of glucose intolerance, are associated with an increased risk for macroangiopathy.

Adult↗
PubMed1999

Breakfast glycaemic response in patients with type 2 diabetes: effects of bedtime dietary carbohydrates.

OBJECTIVES: Bedtime carbohydrate (CHO) intake in patients with type-2 diabetes may improve glucose tolerance at breakfast the next morning. We examined the 'overnight second-meal effect' of bedtime supplements containing 'rapid' or 'slow' CHOs. DESIGN: Randomized cross-over study with three test-periods, each consisting of two days on a standardized diet, followed by a breakfast tolerance test on the third morning. SETTING: The Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden. SUBJECTS: Sixteen patients with type 2 diabetes on oral agents and/or diet. INTERVENTIONS: Two different bedtime (22.00 h) CHO supplements (0.46 g available CHO/kg body weight) were compared to a starch-free placebo ('normal' food regimen). The CHOs were provided as uncooked cornstarch (slow-release CHOs) or white bread (rapid CHOs). RESULTS: On the mornings after different bedtime meals we found similar fasting glucose, insulin, free fatty acid and lactate levels. However, the glycaemic response after breakfast was 21% less after uncooked cornstarch compared to placebo ingestion at bedtime (406 +/- 46 vs 511 +/- 61 mmol min l(-1), P < 0.01). In contrast, it did not differ when the evening meal consisted of white bread (451 +/- 57 mmol min l(-1)) compared to placebo. According to an in vitro analysis, uncooked cornstarch contained approximately 4 times more slowly digestible starch as compared to white bread. CONCLUSIONS: A bedtime meal providing uncooked cornstarch improved breakfast tolerance the next morning while, in contrast, this was not found following a bedtime meal of white bread. The results are consistent, therefore, with the concept that an increased intake of slowly digestible carbohydrates exert an overnight second-meal effect in patients with type 2 diabetes.

Adult↗
PubMed1999

Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in intensively treated type 1 diabetes subjects.

OBJECTIVES: The present study tests two interrelated hypotheses: (1) that bedtime ingestion of uncooked cornstarch exerts a lower and delayed nocturnal blood glucose peak compared with a conventional snack; (2) that bedtime carbohydrate supplement, administered as uncooked cornstarch, prevents nocturnal hypoglycaemia without altering metabolic control in intensively treated type 1 diabetes (IDDM) patients. DESIGN AND SUBJECTS: The above hypotheses were tested separately (1) by pooling and analysing data from two overnight studies of comparable groups of patients with non-insulin dependent diabetes mellitus (NIDDM) (14 and 10 patients, respectively), and (2) by a double-blind, randomized 4-week cross-over study in 12 intensively treated IDDM patients. SETTING: Sahlgrenska University Hospital, Göteborg. Sweden. INTERVENTIONS: (1) Ingestion of uncooked cornstarch and wholemeal bread (0.6 g of carbohydrates kg-1 body weight) and carbohydrate-free placebo at 22.00 h. (2) Intake of uncooked cornstarch (0.3 g kg-1 body weight) and carbohydrate-free placebo at 23.00 h. MAIN OUTCOME MEASURES: (1) Nocturnal glucose and insulin levels; (2) frequency of self-estimated hypoglycaemia (blood glucose [BG] levels < 3.0 mmol L-1) at 03.00 h, HbA1c and fasting lipids. RESULTS: Bedtime uncooked cornstarch ingestion led to a lower (2.9 +/- 0.5 vs. 5.2 +/- 0.6 mM, P = 0.01) and delayed (4.3 +/- 0.6 vs. 2.0 +/- 0.0 h, P < 0.01) BG peak, compared with a conventional snack, in NIDDM patients. Four weeks of bedtime uncooked cornstarch supplement, as compared with placebo, led to a 70% reduction in the frequency of self-estimated hypoglycaemia at 03.00 h (P < 0.05), without affecting HbA1c or fasting lipids in IDDM patients. CONCLUSIONS: Uncooked cornstarch, ingested at bedtime, mimicked the nocturnal glucose utilization profile following insulin replacement, with a peak in blood glucose after 4 h. In IDDM patients, bedtime uncooked cornstarch supplement diminished the number of self-estimated hypoglycaemic episodes, without adversely affecting HbA1c and lipid levels. Hence, bedtime uncooked cornstarch ingestion may be feasible to prevent a mid-nocturnal glycaemic decline following insulin replacement in IDDM and, based on the nocturnal blood glucose profile, may also be preferable compared with conventional snacks.

Adult↗
PubMed1999

Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.

We examined the gene and protein expression of IRS 1 (insulin receptor substrate 1) in adipocytes from two groups of healthy individuals with an increased propensity for non-insulin-dependent diabetes mellitus (NIDDM): those with two first-degree relatives with diabetes and another group with massive obesity. A low expression of IRS 1 (</=50% of the matched control group) was seen in approximately 30% of both groups and these individuals were characterized by insulin resistance and its hallmarks: higher levels of insulin, glucose, and triglycerides. Two individuals with previously unknown NIDDM were diagnosed and both had low IRS 1 expression. Low IRS 1 protein expression was associated with low mRNA levels but not with the common Gly972Arg polymorphism of the IRS 1 gene. Taken together, our present and previous findings show that a low expression of IRS 1 in fat cells predicts insulin resistance and NIDDM. Furthermore, they support the likelihood that an impaired transcriptional activation may play a key role in the pathogenesis of NIDDM.-Carvalho, E., Jansson, P.-A., Axelsen, M., Eriksson, J. W., Huang, X., Groop, L., Rondinone, C., Sjöström, L., Smith, U. Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.

Adult↗
PubMed1997

Topical calcipotriol in childhood psoriasis.

BACKGROUND: The use of topical calcipotriol in adults with psoriasis is safe and effective. OBJECTIVE: Our purpose was to study the efficacy and safety of calcipotriol in children. METHODS: A multicenter, prospective, 8-week, double-blind, parallel group study was conducted in 77 children. Response to treatment was assessed by means of the Psoriasis Area and Severity Index (PASI) in that the intensity of redness, thickness, and scaliness as well as the area involved are scored. The children were 2 to 14 years of age and had stable psoriasis, involving less than 30% of the body surface. Forty-three children were assigned to receive calcipotriol ointment and 34 to receive placebo. Nine children dropped out of the study, six in the calcipotriol-treated group and three in the placebo-treated group. RESULTS: Both treatment groups (calcipotriol and placebo) showed significant improvement in PASI from baseline to the end of treatment, and the difference was not statistically significant. No serious side effects, in particular including those relating to calcium and bone metabolism, were recorded. CONCLUSION: Calcipotriol ointment was statistically significantly more effective than its vehicle in terms of the investigator's overall assessment and reduction in redness and scaliness but not in terms of PASI score.

Administration, Topical↗
PubMed1997

Suppression of the nocturnal free fatty acid levels by bedtime cornstarch in NIDDM subjects.

The aim of the present study was to examine the effects of a large dose of slow-release carbohydrates (CHOs) at bedtime on the nocturnal glucose, insulin and free fatty acid (FFA) levels, and to assess the putative effects on morning fasting and post-prandial glucose levels in patients with moderately controlled non-insulin-dependent diabetes mellitus (NIDDM). Unheated cornstarch (106 g of CHO) or a mixed equicaloric meal (58 g of CHO) was given at 22.00 hours to 10 NIDDM patients. For comparison, the patients were also given a smaller mixed meal at 22.00 hours on a third occasion (17 g of CHO). Compared with the mixed meals, cornstarch led to a slightly elevated early-morning plasma insulin level and a suppression of the nocturnal FFA level (P < 0.05), as well as to a reduced incremental glucose level (IAUC) after breakfast the next morning by approximately 30% (P < 0.05). There was a significant and linear relationship between the nocturnal FFA level and the glucose IAUC after breakfast (r = 0.44, P < 0.02), indicating that the effect may have been mediated by the suppressive effect of cornstarch on nocturnal lipolysis. In summary, bedtime intake of unheated cornstarch in NIDDM subjects is associated with a suppression of the nocturnal FFA levels and a reduced glucose IAUC after breakfast. As the treatment did not improve overall glucose control, studies of the effects of an individually titrated amount of cornstarch are proposed to further explore the putative favourable effects of bedtime cornstarch in the treatment of NIDDM.

Administration, Oral↗
PubMed1995

Lipid intolerance in smokers.

OBJECTIVES: Smokers have recently been shown to be insulin resistant and to exhibit several characteristics of the insulin resistance syndrome (IRS). In this study, we assessed fasting and postprandial lipid levels in healthy, normolipidaemic, chronic smokers and a matched group of non-smoking individuals. DESIGN: A standardized mixed meal (containing 3.78 MJ and 51 g of fat) was given in the morning after an overnight fast. The smokers were either abstinent from tobacco for 48 h or were allowed to smoke freely, including being allowed to smoke six cigarettes during the study. SUBJECTS: Twenty-two middle-aged, healthy male subjects, nine habitual smokers and 13 non-smoking control subjects, were recruited to the study. The smokers had all been smoking at least 10 cigarettes per day for at least 10 years. RESULTS: The smokers exhibited a lipid intolerance in that their postprandial increase in triglyceride levels was more than 50% higher than in the non-smokers' group. This lipid intolerance could not be discerned in the postabsorptive state because the fasting triglyceride levels were the same in both groups, while the smokers had significantly lower high-density lipoprotein (HDL) cholesterol. The peak postprandial triglyceride level correlated closely and negatively with fasting HDL cholesterol, indicating an impaired lipolytic removal capacity in smokers. CONCLUSIONS: Healthy, normotriglyceridaemic smokers exhibit an abnormal postprandial lipid metabolism consistent with lipid intolerance. It is suggested that postprandial hyperlipidaemia is a characteristic trait of the insulin resistance syndrome and that the defect in lipid removal is related to the low HDL cholesterol in this syndrome. The insulin resistance syndrome is likely to be an important reason for the increased propensity for cardiovascular disease in smokers.

Eating↗
PubMedDate not supplied

No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes.

BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.

Blood Glucose↗