Effect of exercise on postprandial insulin responses in Mexican American and non-Hispanic women.

Postprandial insulin responses (integrated area under the curve) to an oral glucose load after a period of aerobic exercise and no exercise (control) were compared in sedentary normoglycemic Mexican American and non-Hispanic women pair-matched (n = 9) on total body fat mass (21.8 +/- 3.5 kg). The age (27.4 +/- 3.0 years), body mass index (BMI) (23.6 +/- 1.4 kg/m2), waist to hip ratio (WHR) (0.85 +/- .02), waist circumference (83.5 +/- 4.5 cm), lean mass (36.2 +/- 1.5 kg), and maximal O2 consumption ([VO2 max] 32.9 +/- 1.6 mL x kg(-1) x min(-1)) were similar, although the centrality index (subscapular/triceps skinfolds) was significantly greater in Mexican Americans (0.88 +/- 0.06 v 0.70 +/- 0.05, P < .01). Exercise (treadmill walking for 50 minutes at 70% VO2 max) and control trials were performed 4 weeks apart and 5 to 12 days after the onset of menstruation. A 75-g oral glucose load was administered 15 hours after the completion of each trial, with the subjects 12 hours postprandial. Blood samples were drawn prior to glucose ingestion (fasting, 0 minutes) and at minutes 15, 30, 60, 90, 120, and 150 postingestion. The postprandial insulin response was calculated using a trapezoidal method. In Mexican Americans, significant (P < .02) reductions in the postprandial insulin response (exercise v control, 6.5 +/- 1.0 v 8.5 +/- 1.4 pmol/L x min x 10(4)) and fasting insulin (exercise v control, 77.4 +/- 7.0 v 88.5 +/- 10.3 pmol/L) occurred after exercise compared with the control condition. In non-Hispanics, neither the postprandial insulin response (exercise v control, 7.2 +/- 1.0 v 6.2 +/- 0.9 pmol/L x min x 10(4)) nor fasting insulin (exercise v control, 77.0 +/- 8.2 v 82.9 +/- 8.9 pmol/L) were significantly different between trials. The postprandial insulin response in the control trial was significantly correlated with the change in the insulin response (control minus exercise) in the 18 women (r = .56, P = .01). No trial or group differences were found for postprandial glucose and C-peptide responses. Mexican American women have a high risk of developing type 2 diabetes, and aerobic exercise may be valuable in the prevention or delay of onset of diabetes by reducing peripheral insulin resistance.     

Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects

BACKGROUND/AIM: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL). SUBJECTS AND METHODS: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin. RESULTS: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0+/-0.4 vs 2.0+/-0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by approximately 35-55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR. CONCLUSION: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.     

Relationship between beta-cell responsiveness and fasting plasma glucose in Caucasian subjects with newly presenting type 2 diabetes.

AIMS : beta-cell responsiveness was related to fasting plasma glucose to gain further understanding of pathophysiology of Type 2 diabetes. METHODS : An insulin secretion model gave fasting beta-cell responsiveness M0 (ability of fasting glucose to stimulate beta-cell) and postprandial beta-cell responsiveness MI (ability of postprandial glucose to stimulate beta-cell) by analysing glucose and C-peptide time-concentration curves sampled every 10-30 min over 240 min during a meal tolerance test (MTT; 75 g CHO, 500 kcal). Caucasian subjects with newly presenting Type 2 diabetes according to WHO criteria (N = 83, male/female: 65 : 18, age: 54 +/- 10 years, body mass index (BMI): 30.9 +/- 5.2 kg/m2, fasting plasma glucose (FPG): 11.0 +/- 3.2 mmol/L; mean +/- SD) and Caucasian healthy subjects (N = 54, m/f: 21 : 33, age: 48 +/- 9 years, BMI: 26.1 +/- 3.7 kg/m2, FPG: 5.1 +/- 0.4 mmol/L) were studied. RESULTS : A continuum inverse relationship between MI and FPG was observed. In the diabetes group, MI was closely related to FPG (rs = -0.74, P < 0.0001) and explained 60% intersubject FPG variability with the use of an exponential regression model. CONCLUSIONS : In newly presenting Type 2 diabetes in Caucasian subjects a close inverse association exists between postprandial beta-cell responsiveness and FPG.     

Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake

CONTEXT: Although dietary protein produces higher acute satiety relative to carbohydrate, the influence of protein source and body mass index (BMI) has not been clearly described. OBJECTIVE: The objective of the study was to assess postprandial responses to different protein sources, compared with glucose, in males with normal and high BMI. DESIGN: This was a randomized, crossover study of four preloads followed by blood sampling (+15, 30, 45, 60, 90, 120, 180 min) and buffet meal. SETTING: The study was conducted at an outpatient clinic. PARTICIPANTS: The study population included 72 men, with a BMI range 20.6-39.9 kg/m(2). INTERVENTIONS: Interventions consisted of liquid preloads (1.1 MJ, 450 ml) containing 50 g whey, soy, gluten, or glucose. MAIN OUTCOME MEASURES: Fasting and postprandial plasma glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (n = 38), ad libitum energy intake, and appetite ratings were measured. RESULTS: Energy intake was 10% lower after all protein preloads, compared with the glucose treatment (P < 0.05), independent of BMI status and protein type. All protein loads prolonged the postprandial suppression of ghrelin (P < 0.01) and elevation of GLP-1 (P < 0.01) and cholecystokinin (P < 0.05). Fasting GLP-1 concentrations [overweight, 17.5 +/- 1.3; lean, 14.7 +/- 0.1 pg/ml (5.2 +/- 0.4 and 4.4 +/- 0.1 pmol/liter, respectively); P < 0.001] and postprandial responses (P = 0.038) were higher in overweight subjects. CONCLUSIONS: Whey, soy, and gluten similarly tend to reduce ad libitum food intake 3 h later in lean and overweight males relative to glucose. Postprandial ghrelin, GLP-1, insulin, and cholecystokinin may contribute to this higher satiety after protein consumption. GLP-1 concentrations are increased in overweight subjects, which may affect satiety responses in this group.     

Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance

OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.     

Fasting and daylong triglycerides in obesity with and without type 2 diabetes

Postprandial hypertriglyceridemia associated with insulin resistance is one of the cardiovascular risk factors in obesity and type 2 diabetes. It is not known whether diabetics have a more pronounced postprandial hypertriglyceridemia than obese subjects. Daylong triglyceridemia, representing postprandial lipemia, was determined in obese subjects with and without type 2 diabetes and in lean subjects. Nineteen type 2 diabetics (F/M: 7/12, body mass index [BMI]: 30.6 +/- 5.4 kg/m(2)), 45 obese nondiabetics (F/M: 16/29, BMI: 29.5 +/- 2.6 kg/m(2)) and 78 lean subjects (F/M: 28/50, BMI: 23.7 +/- 2.2 kg/m(2)) measured capillary triglycerides (TGc) during 3 days on 6 fixed time-points each day in an out-of-hospital situation. Daylong TGc profiles were calculated as mean integrated area under the TGc-curve (TGc-AUC). Fasting plasma TG were higher in diabetics and obese nondiabetics (1.81 +/- 0.79 and 1.77 +/- 0.80 mmol/L) compared with lean subjects (1.23 +/- 0.67 mmol/L, P <.001). TGc-AUC was similarly increased in both diabetics and obese nondiabetics (35.0 +/- 12.1 and 35.2 +/- 10.6 mmol.1 h/L) compared with lean controls (25.5 +/- 12.0 mmol.1 h/L, P <.001). Self-reported energy intake was not significantly different between the groups. Fasting TGc (r =.87, P <.001) and waist circumference (r =.51, P <.001) were the parameters best associated with TGc-AUC. Using stepwise multiple regression analysis, fasting TGc, BMI, total cholesterol, and high-density lipoprotein (HDL) cholesterol were the best predictors of TGc-AUC, explaining 77% of the variation. The cut-off level for "normal" TGc-AUC, calculated as the 75th percentile of TGc-AUC in lean subjects, was 30.7 mmol.1 h/L and corresponded with a fasting TGc of 1.8 mmol/L (eg, 1.6 mmol/L in plasma), calculated using univariate regression analysis. In conclusion, daylong triglyceridemia is similarly increased in diabetics and obese nondiabetics compared with lean subjects. Fasting TG and central obesity largely determine daylong triglyceridemia, independent of the presence of type 2 diabetes. Decreasing fasting plasma TG below 1.6 mmol/L could lead to a normalization of postprandial lipemia in obese subjects with and without diabetes.     

Increase in postprandial serum insulin levels in epileptic patients with valproic acid therapy

A significant weight gain and increase in serum leptin levels in the course of antiepileptic treatment with valproic acid (VPA) has been described in several clinical studies. With respect to the long treatment period in antiepileptic therapy, these side effects might increase insulin resistance and metabolic risk factors. We have studied clinical and laboratory effects of VPA treatment in a cohort of female patients (n = 22) and in patients treated with carbamazepine (CBZ) or lamotrigine monotherapy (n = 21). All study participants underwent an oral glucose tolerance test (OGTT) with 75 g glucose. Body mass index (BMI) in the VPA group was higher (28.1 +/- 3.6 kg/m(2)) than in the control group (23.9 +/- 3.7 kg/m(2)) (P <.039). While plasma glucose, serum leptin, insulin, and C-peptide levels did not differ significantly between the study groups in the fasting state, postprandial (pp) insulin and proinsulin levels were found to be significantly higher in the VPA than in the control group. In the course of the OGTT, serum insulin levels reached their peak values 1 hour postprandially with 68.8 +/- 10.0 microU/mL in the VPA group and 49.8 +/- 11.2 microU/mL in the control group (P <.042). After 2 hours, the corresponding serum insulin levels were 48.5 +/- 25.2 microU/mL and 34.1 +/- 17.2 microU/mL (P <.048) and the proinsulin levels 52.5 +/- 30.2 pmol/L and 29.5 +/- 12.0 pmol/L (P <.017). While BMI values in the non-VPA group showed a significant correlation only with the fasting values of insulin, proinsulin, and C-peptide, the BMI values of the VPA-treated group were also positively related to the 2-hour pp levels of insulin (R =.690; P <.001), proinsulin (R =.667; P <.001) and C-peptide (R =.502; P <.017). VPA is a fatty acid derivative, competes with free fatty acids (FFA) for albumin binding, and acts as a gamma aminobutyric acid (GABA)-ergic agonist, mechanisms, which are known to be involved in pancreatic beta-cell regulation and insulin secretion. Therefore, it might be suspected that VPA therapy is associated with increased glucose stimulated pancreatic secretion and thus a higher body weight in the VPA group.     

Antidiabetogenic action of glucagon-like peptide-1 related to administration relative to meal intake in subjects with type 2 diabetes

OBJECTIVE: To establish the antidiabetogenic effect of glucagon-like peptide-1 (GLP-1) when differently administered relative to meal intake in subjects with type 2 diabetes. DESIGN: The study was a placebo-controlled comparison with random assignment to treatment sequence. A 3-h stepwise infusion of GLP-1 (17 nmol) was started either at the onset of a standard meal (550 kCal) (A) or at 30 min (B) or 60 min (C) after the start of the meal. SETTING: The study was conducted at a university hospital. SUBJECTS: Eight patients with type 2 diabetes (four women and four men), age 62 +/- 3.9 years (range 47-74 years), weight 79.8 +/- 5.4 kg (range 62-104 kg), BMI 26.2 +/- 1.3 kg m(-2) (range 21-31 kg m(-2)), diabetes duration 10.5 +/- 2.0 years (range 3-19 years) and HbA1c levels 6.1 +/- 0.3% (range 4.7-7.7%) participated in the study. All patients were treated with oral sulphonylureas. RESULTS: Glucagon-like peptide-1 significantly lowered postprandial glycaemia by a similar degree in all three situations versus the control meal (P < 0.05). Postprandial insulin levels were not different in the four experimental series, whereas the postprandial glucagon levels were significantly lowered by GLP-1 in (A) and (B) (P < 0.03) but not in (C). Gastric emptying, as determined by the paracetamol test, was retarded by GLP-1 only in (A) (P < 0.01), but not affected in (B) or (C). CONCLUSIONS: GLP-1 reduced postprandial hyperglycaemia in subjects with type 2 diabetes regardless of administration at the onset of meal intake or at 30 or 60 min after start of meal intake, although the mechanism of the antidiabetogenic action of GLP-1 depended on administration versus meal intake. Thus, when administered at the start of a meal, GLP-1 was antidiabetogenic mainly through retarding gastric emptying, whereas when given at 30 or 60 min after meal ingestion, changes in islet hormone secretion seem to be predominant.     

Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus.

The assessment of the postprandial state in diabetes mellitus has gained importance due to postprandial hyperglycemia being considered as an independent risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular dysfunction through the alteration of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6 years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/- 2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI: 25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate) levels did not differ between the diabetic and control group, cGMP levels were found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/- 0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS) was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p = 0.004). The diabetic subgroup without late complications had significantly higher nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6 vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were similar. The control subjects responded to the test meal with an increase in the cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic group no change was detected. Postprandial nitrite/nitrate levels decreased in both groups, they were significantly lower in the diabetic group. There was no difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the diabetic subgroups. Postprandial glucose levels showed a significant negative correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The results suggest that in subjects with type 1 diabetes mellitus NO might have an impaired ability to induce cGMP production in the fasting state prior to the development of late specific complications or microalbuminuria under hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere with endothelial NO action, as shown by the decreased nitrite/nitrate and unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP pathway both in the fasting and postprandial state that was shown in patients without diabetic complications may be an early sign of hyperglycemia induced vascular damage in type 1 diabetes mellitus.     

Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes

CONTEXT: Gastric bypass surgery (GBP) results in rapid weight loss, improvement of type 2 diabetes (T2DM), and increase in incretins levels. Diet-induced weight loss also improves T2DM and may increase incretin levels. OBJECTIVE: Our objective was to determine whether the magnitude of the change of the incretin levels and effect is greater after GBP compared with a low caloric diet, after equivalent weight loss. DESIGN AND METHODS: Obese women with T2DM studied before and 1 month after GBP (n = 9), or after a diet-induced equivalent weight loss (n = 10), were included in the study. Patients from both groups were matched for age, body weight, body mass index, diabetes duration and control, and amount of weight loss. SETTING: This outpatient study was conducted at the General Clinical Research Center. MAIN OUTCOME MEASURES: Glucose, insulin, proinsulin, glucagon, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP)-1 levels were measured after 50-g oral glucose. The incretin effect was measured as the difference in insulin levels in response to oral and to an isoglycemic iv glucose load. RESULTS: At baseline, none of the outcome variables (fasting and stimulated values) were different between the GBP and diet groups. Total GLP-1 levels after oral glucose markedly increased six times (peak:17 +/- 6 to 112 +/- 54 pmol/liter; P < 0.001), and the incretin effect increased five times (9.4 +/- 27.5 to 44.8 +/- 12.7%; P < 0.001) after GBP, but not after diet. Postprandial glucose levels (P = 0.001) decreased more after GBP. CONCLUSIONS: These data suggest that early after GBP, the greater GLP-1 and GIP release and improvement of incretin effect are related not to weight loss but rather to the surgical procedure. This could be responsible for better diabetes outcome after GBP.     

Preferential release of proinsulin relative to insulin in non-insulin-dependent diabetes mellitus

A radioimmunoassay, using an antiserum that is specific for human proinsulin, has been used to study the response of serum proinsulin to low (25 g) and high (75 g) oral glucose loads in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Diabetic patients were treated by diet only (N = 8) or were receiving oral anti-hyperglycemic agents (N = 8) and therapy was not interrupted during the study. In the fasted state, proinsulin concentrations were higher (P less than 0.05) in the drug-treated patients (31 +/- 3 pmol/l (SEM)) compared with age- and weight-matched healthy subjects (22 +/- 2 pmol/l; N = 10), but concentrations in the diet-treated patients 25 +/- 3 pmol/l) were not significantly different. Following 25 g and 75 g glucose loads, the rises in serum immunoreactive insulin and C-peptide concentrations in both groups of diabetic patients were impaired and delayed relative to those in the control subjects. The responses of serum proinsulin, however, were not significantly different in the NIDDM patients compared with controls at any time point up to 180 min except in the case of drug-treated patients receiving 25 g of glucose who had elevated (P less than 0.05) proinsulin concentrations at 150 min and 180 min after ingestion. It is concluded that NIDDM is not associated with an exaggerated release of proinsulin in response to glucose compared with healthy subjects, but the islets have maintained the ability to release proinsulin better than the ability to release insulin.     

A three-day insulin-induced normoglycemia improves carbohydrate oxidation in type 2 diabetic subjects

Two months of a better glycemic control improve carbohydrate oxidation in type 2 diabetes. However, this benefit is uncertain for a shorter duration. We tested the effect of 3 days of normoglycemia induced by an insulin infusion. Ten type 2 diabetic subjects (body mass index [BMI], 30.0 +/- 1.1; glycosylated hemoglobin [HbA(1C)], 10.1 +/- 0.5) were studied twice, before and after normal glucose levels were maintained by a 72-hour intravenous insulin infusion. Indirect calorimetry was performed 1 hour before (basal) and during the 3 hours after (postprandial) the ingestion of a standard meal (carbohydrates, 72 g; fat, 21 g; protein, 32 g), at noon. Carbohydrate storage was calculated as ingested carbohydrate - (postprandial glycosuria + suprabasal postprandial carbohydrate oxidation). After normoglycemia, glucose and triglyceride levels were decreased (basal glucose, 13.8 +/- 1.1 mmol/L to 8.8 +/- 0.5; postprandial, 14.9 +/- 0.9 to 11.0 +/- 0.5; basal triglycerides, 2.2 +/- 0.1 mmol/L to 1.6 +/- 0.2; postprandial, 2.7 +/- 0.2 to 1.9 +/- 0.2; all P <.01), C peptides were unchanged. Glycosuria (before, 0.30 mg/kg/min) was abolished after normoglycemia. Basal carbohydrate, lipid, protein oxidation, and energy production rates were unchanged. Postprandial carbohydrate oxidation was increased after normoglycemia (before, 1.33 +/- 0.38 mg/kg/min; after, 1.77 +/- 0.42; P <.05). Lipid oxidation and plasma free fatty acids (FFA) tended to be more suppressed by the meal after normoglycemia (not significant [NS]). Carbohydrate storage (before, 67,5 +/- 4.6 g; after, 65.7 +/- 3.6; NS) and diet-induced thermogenesis did not change after normoglycemia. Short-term insulin-induced normoglycemia improves the postprandial oxidation of carbohydrates, but not their storage.     

Differential postprandial lipoprotein responses in type 2 diabetic men with and without clinical evidence of a former myocardial infarction

Postprandial lipemia plays an important role in the development of coronary heart disease through an elevation of triglyceride-rich lipoproteins. In type 2 diabetic male subjects, our aim was to compare postprandial lipemia in a high-risk population with former myocardial infarction (MI) with that of a lower risk population free of clinically detectable heart disease. 32 male type 2 diabetic subjects were included in the study. We matched 17 cases with a verified history of MI with 15 controls according to age, BMI, HbA1c, diabetes duration, smoking, and treatment of diabetes. Ongoing metformin, insulin, or lipid lowering pharmacological treatment were exclusion criteria. After a maximal exercise tolerance test and echocardiography, the subjects underwent a hyperinsulinemic, euglycemic clamp and a vitamin A fat loading test. Plasma triglyceride levels in the case group were significantly higher after 360 minutes (4.6 +/- 3.1 vs. 2.8 +/- 1.8 mmol/l, p = 0.04) and 480 minutes (3.6 +/- 2.2 vs. 2.4 +/- 2.4 mmol/l, p = 0.03), as was the incremental Area Under the Curve (iAUC) for the whole period (560 +/- 452 vs. 297 +/- 214 mmol x 480 min./l; p = 0.048). In addition, the retinyl palmitate responses in the chylomicron-fraction from the case group were significantly higher (iAUC 311,502 +/- 194,933 vs. 187,004 +/- 102,928 ng x 480 min./ml; p = 0.035). Type 2 diabetic males with prior MI had higher postprandial triglyceride-rich lipoprotein responses than those without MI, indicating that high responses may be a marker for a high-risk population.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS:: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance.

Proinsulin release is increased relative to insulin secretion in subjects with type 2 diabetes, indicative of islet dysfunction. However, it has not been conclusively shown whether there is an increased relative proinsulin release in subjects with impaired glucose tolerance (IGT), i.e. whether it precedes the development of diabetes. We therefore determined the proinsulin to insulin ratios in the fasting state and after acute stimulation of insulin secretion in 23 postmenopausal women, aged 61-62 yr (mean +/- SD, 61.7 +/- 0.5 yr). Ten women had normal glucose tolerance (NGT), and 13 had IGT. The groups were matched for insulin sensitivity and did not differ in body mass index. Proinsulin and insulin secretion were measured after arginine stimulation (5 g, i.v.) at three glucose levels (fasting, 14 mmol/L, and >25 mmol/L), and the acute insulin (AIR(arg)) and proinsulin responses (APIR(arg)) were calculated as the mean 2-5 min postload increase. At fasting glucose, levels of insulin, proinsulin, or the proinsulin/insulin ratio (13.6 +/- 5.0% vs. 11.1 +/- 2.7%; P = NS) did not differ between NGT and IGT. Although the AIR(arg) values were decreased in the IGT group at all glucose levels (P < 0.05), the absolute proinsulin levels and the APIRs(arg) were similar between IGT and NGT women. Therefore, the IGT women had higher proinsulin/insulin ratios at 14 mmol/L (10.7 +/- 4.4% vs. 6.4 +/- 1.8%; P = 0.006) and more than 25 mmol/L glucose (11.4 +/- 5.2% vs. 6.7 +/- 2.1%; P = 0.007). The IGT group had increased APIR(arg)/AIR(arg) at fasting (2.2 +/- 1.4% vs. 1.3 +/- 0.6%; P = 0.047) and more than 25 mmol/L glucose (3.5 +/- 1.6% vs. 2.3 +/- 0.7%; P = 0.037). We conclude that women with IGT exhibit increased relative proinsulin secretion, suggesting a defect in the intracellular proinsulin processing before diabetes develops.     

Postprandial silent ischaemia following a fatty meal in patients with recently diagnosed coronary artery disease

Silent myocardial ischaemia (SI) is recognised as an important prognostic factor in patients with coronary artery disease (CAD). Postprandial angina is related to severity of CAD. The effect of postprandial metabolic changes in the pathogenesis of SI is unclear. We studied the postprandial changes in glucose, insulin and triglyceride, and non-esterified fatty acids (NEFA) in relation to postprandial SI and exercise capacity, in patients with CAD. Forty elderly volunteers (63 +/- 1 years) mean age +/- s.e.m., with a history of angina were selected on the basis of a Rose questionnaire and a positive exercise stress test (modified Bruce protocol). The test meal contained 45% fat. The meal was consumed at 9.00 am and hourly blood samples were taken for glucose, insulin, triglyceride and NEFA. Continuous Holter monitoring for SI was conducted using a Spacelabs 2000 monitor. Twenty-five percent of the subjects had episodes of silent ischaemia. Postprandial glucose, insulin, triglyceride, and NEFA were not significantly different in the patients with SI (group 1, n = 10) compared with those without SI (group 2, n = 30). The mean exercise time was 6.1 +/- 0.8 min in group 1 compared with 6.8 +/- 0.5 minutes in group 2 (P = 0.48). The time to onset of ST depression during exercise test was also not significantly different in the two groups. The occurrence of postprandial SI cannot be related to changes in plasma levels of glucose, triglyceride, insulin, and NEFA. The explanation is not apparent from this study but may relate to a haemodynamic changes such as mesenteric steal. Journal of Human Hypertension (2000) 14, 391-394     

Reduced leptin concentrations in subjects with type 2 diabetes mellitus in Sudan

Differences have been observed in the relationship between leptin and metabolic perturbations in glucose homeostasis. Because no information is available from indigenous African populations with diabetes, the purpose of this study was to investigate the possible associations between leptin and different clinical and biochemical characteristics of a large group of subjects with type 2 diabetes mellitus in Sudan. A total of 104 (45 men and 59 women) consecutive type 2 diabetes patients and 75 control subjects (34 men and 41 women) were studied. The body mass index (BMI), blood glucose, serum insulin, and proinsulin were measured and related to serum leptin concentrations. Leptin was higher in females than in males and correlated significantly to BMI. The main novel finding was that serum leptin was significantly lower in diabetic subjects compared with controls in both females (P =.0001) and males (P =.019), although BMI did not differ between diabetic and nondiabetic subjects. Diabetic subjects treated with sulphonylurea (n = 81) had lower BMI than those treated with diet alone or other hypoglycemic drugs (n = 23) (P =.0017), but there was no difference in leptin levels between the 2 groups after adjustment for BMI (P =.87). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =.018) and insulin resistance (P =.038), whereas in control subjects, leptin correlated with insulin resistance (P =.0016), but not with beta-cell function. Diabetic subjects had higher proinsulin levels (P =.0031) and higher proinsulin to insulin ratio (P =.0003) than nondiabetic subjects. In univariate analysis, proinsulin showed a weak correlation to leptin (P =.049). In conclusion, we show in a large cohort of Sudanese subjects with type 2 diabetes that circulating leptin levels are lower in diabetic subjects than in controls of similar age and BMI. The lower serum leptin in diabetic subjects may be a consequence of differences in fat distribution.     

Effect of ageing and diabetes on glucose-dependent insulinotropic polypeptide and dipeptidyl peptidase IV responses to oral glucose.

AIMS: Glucose-dependent insulinotropic polypeptide (GIP) acts on the pancreas to potentiate glucose-induced insulin secretion (enteroinsular axis). GIP is rapidly inactivated in vivo by the enzyme dipeptidyl dipeptidase IV (DPP-IV). The current studies were designed to examine the effect of ageing, obesity and diabetes on GIP and DPP-IV responses to oral glucose. METHODS: Healthy controls (nine middle-aged, age 42 +/- 2 years, body mass index (BMI) 33 +/- 1 kg/m2; nine elderly, age 71 +/- 1 years, BMI 30 +/- 1 kg/m2) and patients with Type 2 diabetes (12 middle-aged, age 44 +/- 2 years, BMI 34 +/- 2 kg/m2; 19 elderly, age 74 +/- 1 years, BMI 31 +/- 1 kg/m2) underwent a 3-h oral glucose tolerance test (OGTT) (glucose dose 40 g/m2). RESULTS: Insulin responses were similar in elderly controls and patients with diabetes, but were lower in middle-aged patients with diabetes than in controls (308 +/- 65 vs. 640 +/- 109 pM, P < 0.05). GIP responses were similar in controls and patients with diabetes in each age group, but were higher in elderly controls (middle-aged 45 +/- 13; elderly 112 +/- 13 pM, P < 0.01) and patients with diabetes (middle-aged 55 +/- 10; elderly 99 +/- 10 pM, P < 0.01). DPP-IV levels were lower in patients with diabetes in both middle-aged (control 0.241 +/- 0.015; diabetes 0.179 +/- 0.017 delta OD/20 min, P < 0.05) and elderly groups (control 0.223 +/- 0.019; diabetes 0.173 +/- 0.010 delta OD/20 min, P < 0.05). CONCLUSIONS: It was concluded that ageing in obese subjects is associated with enhanced GIP responses to oral glucose. In addition, DPP-IV activity is reduced in middle-aged and elderly obese patients with diabetes.     

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.