Diurnal changes in plasma lipoproteins in normal subjects and diabetics

Summary Significant diurnal variations in levels of total plasma cholesterol, HDL cholesterol and LDL cholesterol were found in the majority of 12 normals, 13 maturity onset and 14 insulin requiring diabetics. The variations in total cholesterol and its lipoprotein subfraction were more marked in diabetics. These variations were not correlated in either diabetic group with glucose control as assessed by the level of glycosylated haemoglobin. The significance of the diurnal changes in total plasma cholesterol and the lipoprotein subfractions in relation to arteriovascular disease is discussed.     

Ambulatory and exercise-induced blood pressure responses in type I diabetic patients and normal subjects

We evaluated the ambulatory blood pressure (BP) readings during daily activities and compared the values with the casual office BPs in 12 type I diabetic patients and 12 age-matched, non-diabetic normal controls. The BP responses to 750 kpm/min exercise work load on bicycle ergometer were also evaluated in all the subjects. The mean ambulatory BPs were significantly higher in the diabetic patients compared with non-diabetic subjects. However, the ambulatory and casual office BPs were remarkably similar in each group. Mean peak exercise BPs were higher in the diabetics, but significantly so for diastolic BP (P less than 0.05) and mean arterial pressure (MAP) (P less than 0.01). The mean ambulatory MAP significantly correlated with the casual office MAP in both the diabetics (r = 0.75, P less than 0.005) and non-diabetics (r = 0.58, P less than 0.02). A significantly positive relationship (r = 0.87, P less than 0.001) existed between the ambulatory and peak exercise MAP in the diabetics, but not in the non-diabetic subjects. The mean peak exercise BP responses were significantly (P less than 0.01) higher in the diabetic patients with proliferative retinopathy vs. those with non-proliferative retinopathy. We conclude that casual office BPs reflect the ambulatory values in both diabetics and non-diabetics. Exaggerated BP responses to exercise are found in diabetic patients, especially in the presence of proliferative retinopathy. These findings are suggestive of possible defects in the cardiovascular, autonomic and autoregulatory mechanisms that maintain a normal MAP during daily stresses and exercise in the diabetic patients.     

Serum and erythrocyte magnesium levels in type I and type II diabetics

Summary Serum and red blood cell magnesium (RBC-Mg) concentrations of 195 type I and III type II diabetic outpatients with different degree of control and 40 control subjects have been evaluated using atomic absorption spectrophotometry. In the total group, no significant difference in serum and RBC-Mg levels in type I and II diabetic outpatients could be found. However, poor control was often associated with lower serum magnesium levels. A negative correlation was found between serum magnesium levels and HbA₁. A particular group of male patients with severe macroangiopathy showed high RBC-Mg levels; this finding was probably due to atherosclerotic and hypertensive renal involvement.     

Sugars and fat have different effects on postprandial glucose responses in normal and type 1 diabetic subjects

Background and aims

We aimed to determine the effects on glycemic responses and potential risk of hypoglycaemia in type 1 diabetic subjects of replacing half the starch in a meal with sugars, and of adding fat to the low-sugar and high-sugar meals.

Methods and results

We studied overnight fasted subjects with type 1 diabetes (n = 11) and age-, BMI- and ethnicity-matched controls (n = 11) using a 2 × 2 factorial design. The low-sugar/low-fat meal was 110 g white-bread. In the high-sugar/low-fat meal half the white-bread starch replaced by sugars (jam and orange juice). The high-fat meals consisted of the low-fat meals plus 20 g fat (margarine). The significance of the main effects of sugars and fat and the sugar × fat, group × sugar and group × fat interactions were determined by ANOVA. In control and diabetic subjects, respectively, high-sugar significantly reduced time to peak rise by 13% (P = 0.004) and 32% (P = 0.004; group × sugar: P = 0.01) and increased peak rise by 14% and 10% (ns). Adding fat increased time to peak rise by 17-19% in both groups (P = 0.003), reduced peak rise by 31% in normal (P < 0.001) but increased peak rise in diabetic subjects by 3% (ns) (group × fat: P = 0.022). Blood glucose nadir and occurrence of hypoglycaemia were similar among the 4 meals.

Conclusions

In type 1 diabetes, insulin adjustment to avoid hypoglycemia may be useful for meals in which the proportion of carbohydrate absorbed as glucose is <0.75, however the precise level which increases hypoglycaemic risk requires further research. The results suggest that people with type 1 diabetes should not be advised to add fat to meals to reduce glycemic responses.     

American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus

BACKGROUND: Despite a lack of medical evidence to support its therapeutic efficacy, the use of herbal medicine has increased considerably. Ginseng, one of the most widely used herbs, is hypothesized to play a role in carbohydrate metabolism and diabetes mellitus. We therefore undertook a preliminary short-term clinical study to assess whether American ginseng (Panax quinquefolius L) affects postprandial glycemia in humans. DESIGN: On 4 separate occasions, 10 nondiabetic subjects (mean [+/-SD] age, 34+/-7 years; mean [+/-SD] body mass index [BMI], 25.6 +/- 3 kg/m2) and 9 subjects with type 2 diabetes mellitus (mean [+/-SD] age, 62 +/- 7 years; mean [+/-SD] BMI, 29 +/- 5 kg/m2; mean [+/-SD] glycosylated hemoglobin A1c, 0.08+/-0.005) were randomized to receive 3-g ginseng or placebo capsules, either 40 minutes before or together with a 25-g oral glucose challenge. The placebo capsules contained com flour, in which the quantity of carbohydrate and appearance matched the ginseng capsules. A capillary blood sample was taken fasting and then at 15, 30, 45, 60, 90, and 120 (only for subjects with type 2 diabetes mellitus ) minutes after the glucose challenge. RESULTS: In nondiabetic subjects, no differences were found in postprandial glycemia between placebo and ginseng when administered together with the glucose challenge. When ginseng was taken 40 minutes before the glucose challenge, significant reductions were observed (P<.05). In subjects with type 2 diabetes mellitus, the same was true whether capsules were taken before or together with the glucose challenge (P<.05). Reductions in area under the glycemic curve were 18%+/-31% for nondiabetic subjects and 19+/-22% and 22+/-17% for subjects with type 2 diabetes mellitus administered before or together with the glucose challenge, respectively. CONCLUSIONS: American ginseng attenuated postprandial glycemia in both study groups. For nondiabetic subjects, to prevent unintended hypoglycemia it may be important that the American ginseng be taken with the meal.     

Metabolic and hormonal effects of muscular exercise in juvenile type diabetics

Summary Metabolic and hormonal effects of muscular exercise were studied in juvenile-type diabetics in relation to the prevailing degree of metabolic control and compared with those in healthy control subjects. Two groups of diabetic patients, one in moderate metabolic control and one in ketosis due to insulin withdrawal, were subjected to a 3 hour bicycle ergometer test of comparable, mild work intensity. In both groups of diabetics the exercise-induced rise in blood lactate was similar, but was significantly higher than in control subjects. Blood alanine levels showed a transient, significant rise in both diabetic groups, but not in controls. Blood concentrations of branch-chained amino acids remained unchanged. In the moderately controlled diabetics, exercise induced a marked fall of blood glucose and increases in blood levels of free fatty acids (FFA), ketone bodies and glucagon, which were comparable to the exercise effects in normal controls. In ketotic diabetics, however, exercise led to an additional rise in blood glucose concentration and to increases in ketone body, glucagon and cortisol levels. Significant correlations were found between the exercise effect on blood glucose and initial blood levels of glucose, FFA, ketone bodies and branch chained amino acids: pre-exercise values of above 325 mg/dl glucose, 1173 mol/l FFA, 2.13 mmol/l ketone bodies and 0.74 mmol/l branch chained amino acids led to increased blood glucose levels on exercise, whereas below these limits glucose fell during the exercise test. These findings seem to be, at least in part, explained by the hypothesis of a permissive effect of insulin during stimulation of muscle glucose uptake by exercise. The increased circulating levels of glucagon and cortisol during exercise in ketotic diabetics might represent additional hyperglycaemic and, probably more important, lipolytic and ketogenic stimuli. The results suggest that in moderately controlled, non-ketotic diabetics blood glucose falls during exercise; in ketotic, relatively insulin deficient patients, muscular activity has adverse metabolic and hormonal effects: a further increase in blood glucose, plasma glucagon and cortisol and a rapid aggravation of ketosis.     

Comparative effects of phenformin,metformin and glibenclamide on metabolic rhythms in maturity-onset diabetics

Summary Twelve hour metabolic rhythms have been performed on six maturity-onset diabetic subjects during successive periods of therapy with phenformin, metformin, and glibenclamide. Moderate control of blood glucose concentration was achieved with phenformin and metformin, the lowest concentrations being found with glibenclamide. Mean blood lactate concentration was grossly elevated during phenformin therapy, moderately elevated with metformin and normal during glibenclamide treatment. Similar patterns were found for the lactate/pyruvate ratio, alanine, glycerol and ketone bodies. Serum triglyceride concentrations were significantly higher during phenformin treatment than with the other two regimes. Serum insulin concentration was higher on glibenclamide than with either biguanide. Most of these effects of the biguanides could be accounted for by an inhibitory effect on hepatic gluconeogenesis. It is concluded that the use of biguanides as hypoglycaemic agents in diabetes is associated with the production of multiple metabolic abnormalities.     

The effects of intravenous clomipramine on neurohormones in normal subjects

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethylclomipramine, a metabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.     

Nailfold capillaroscopy in type I diabetics with vasculopathy and limited joint mobility

The nailfold capillary pattern of 48 Type I diabetic patients with longstanding disease and of 15 normal controls was studied using the technique of widefield nailfold capillaroscopy. Twenty-six diabetic patients had documented vascular disease (retinopathy) and 27 had flexion contractures of the hand. No distinctive morphologic capillary lesions were observed in any diabetic patient, nor were any differences in capillary loop number or density found between the diabetic and control groups. While vascular disease is a prominent feature of diabetes, it is not reflected in the appearance of the nailfold capillary pattern.     

Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas (AEP) and in normal subjects

In order to evaluate the effects of moderate alcohol intake on intermediate metabolites, five normal subjects and five euglycemic insulin-dependent diabetics (IDDM) were administered two different isocaloric diets; in one diet 35% of the caloric intake consisted of red wine. The insulin-dependent diabetics were connected to an artificial endocrine pancreas (AEP), and glucose levels were continuously monitored. Blood lactate, pyruvate, acetoacetate (AcAc), 3-hydroxybutyrate (3-OHB), glycerol, free fatty acids (FFA), and alanine levels were measured over a 15-hour period from 9 AM to 12 PM. The results showed that alcohol intake did not significantly influence the glucose profiles in either group (111 +/- 4 mg/100 ml versus 110 +/- 4 mg/100 ml for IDDM; 72 +/- 2 mg/100 ml versus 82 +/- 3 mg/100 ml for controls, 15-hour mean +/- SEM), but in both groups it induced a marked increased in the levels of lactate (1.115 +/- 0.067 mM/liter with alcohol versus 0.706 +/- 0.031 mM/liter without alcohol for IDDM; 0.847 +/- 0.052 mM/liter with alcohol versus 0.666 +/- 0.035 mM/liter without alcohol for controls), in the lactate/pyruvate ratio (24.04 +/- 2.12 with alcohol versus 11.42 +/- 0.20 without alcohol for IDDM; 20.84 +/- 2.16 with alcohol versus 11.62 +/- 0.27 without alcohol for controls), in the levels of 3-OHB (0.081 +/- 0.007 mM/liter with alcohol versus 0.046 +/- 0.003 mM/liter without alcohol for IDDM; 0.067 +/- 0.007 mM/liter with alcohol versus 0.025 +/- 0.002 mM/liter without alcohol for controls) and in the 3-OHB/AcAc ratio (1.452 +/- 0.153 with alcohol versus 0.599 +/- 0.036 without alcohol for IDDM; 1.723 +/- 0.198 with alcohol versus 0.439 +/- 0.040 without alcohol for controls) because of a more reduced redox state. Alcohol intake during meals depressed alanine concentration, while glycerol levels showed a transient increase. Reduced blood FFA concentrations after alcohol intake were observed only in controls. This study demonstrates that moderate alcohol intake with meals also affects intermediate metabolites despite euglycemia. These effects were similar both in normal subjects and in IDDM, even if the harmful effects of alcohol may be enhanced by poor metabolic control in the latter.     

Blood pressure, insulin, and glycemia in nondiabetic subjects

The relation of blood pressure to fasting (basal) insulin and glycosylated hemoglobin (hemoglobin A1) was examined in 248 nondiabetic subjects (137 women and 111 men). None of the subjects was taking antihypertensive medication. There were statistically significant associations of systolic and diastolic blood pressure with insulin levels (r = 0.24, p less than 0.01; r = 0.30, p less than 0.01) and hemoglobin A1 levels (r = 0.28, p less than 0.001; r = 0.22, p less than 0.05) in women. These blood pressure indexes were also related to insulin levels in men (r = 0.23, p less than 0.05; r = 0.02, p less than 0.05). In a multiple regression analysis, the association between blood pressure and insulin level was diminished with an allowance for adiposity; however, it remained statistically significant. These data indicate that blood pressure is related to insulin levels in nondiabetic subjects and suggest that insulin may be a physiologic determinant of blood pressure.     

Acute dietary effects on diurnal plasma lipids in normal subjects

The effects of different dietary carbohydrates and different dietary fats as well as of differently spaced dietary constituents on 24-h plasma free fatty acids and triglycerides were determined in healthy young males. If, in an isocaloric diet containing 15-20% protein, 37% fat and 43--48% carbohydrates, sucrose is compared with glucose, 24-h plasma triglycerides are significantly higher with the former carbohydrate. When palm oil (mainly 16 : 0 fatty acids) is compared with olive oil (mainly 18 : 1 fatty acids), 24-h triglycerides are significantly higher with the latter. If the carbohydrate component of a mixed meal is removed, alimentary lipemia is considerably greater. Our findings supplement long term studies regarding the effect of different dietary fats and carbohydrates on plasma lipids and allow calculation of "upper normal limits" for 24-h plasma triglycerides and free fatty acid patterns on isocaloric diets of "prudent" composition.     

Biosynthetic human insulin improves postprandial glucose excursions in type I diabetics

To determine if the more rapid absorption of subcutaneously administered human insulin, as compared with animal insulin, would result in an improved postprandial metabolic response, ten persons with type I diabetes mellitus were studied during a fixed meal. Plasma glucose and insulin concentrations were compared after subcutaneous injections of 0.2 U/kg body weight of regular biosynthetic human insulin or regular purified pork insulin in a double-blind randomized crossover trial. Meal glycemic excursions improved after the administration of biosynthetic human insulin, when compared with purified pork insulin (p less than 0.05 at 150, 180, and 210 minutes postprandially). Serum free immunoreactive insulin concentrations were significantly higher after injections of biosynthetic human insulin, and the rate of incremental rise during the first 30 minutes was also greater. Insulin antibody studies showed a strong negative correlation between peak insulin levels and the association constant for the high-affinity-binding insulin antibodies. We conclude that biosynthetic human insulin is more rapidly absorbed after subcutaneous injection than is purified pork insulin, a characteristic that results in improved postprandial metabolic control.     

The effects of smoking on the signal-averaged electrocardiogram in normal subjects

Tobacco smoking increases the risk of sudden cardiac death, possibly by altering the substrate for propagation or sustainment of ventricular tachyarrhythmias. To test this hypothesis, 15 long-term smokers without known coronary artery disease abstained from tobacco smoking for 12 h, after which they underwent SAECG before, 15 min after and 30 min after smoking two cigarettes. Other than minor lengthening of filtered QRS duration, no significant change in time-domain SAECG parameters was noted. We conclude that late potentials are not produced by cigarette smoking and that ventricular arrhythmia substrate as measured by SAECG variables is not worsened in long-term smokers without evidence of coronary artery disease.     

Pharyngeal pressure and flow effects on genioglossus activation in normal subjects.

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnea syndrome. Substantial data support the role of local mechanisms in mediating pharyngeal dilator muscle activation in normal humans during wakefulness. Using a recently reported iron lung ventilation model, we sought to determine the stimuli modulating genioglossus activity, dissociating the influences of pharyngeal negative pressure, from inspiratory airflow, resistance, and CO(2). To achieve this aim, we used two gas densities at several levels of end-tidal CO(2) and a number of intrapharyngeal negative pressures. The correlations between genioglossus electromyography (GGEMG) and epiglottic pressure across a breath remained robust under all conditions (R values range from 0.71 +/- 0.07 to 0.83 +/- 0.05). In addition, there was no significant change in the slope of this relationship despite variable gas density or CO(2) levels. Although flow also showed strong correlations with genioglossus activity, there was a significant change in the slope of the GGEMG/flow relationship with altered gas density. For the group averages across conditions (between breath analysis), the correlation with GGEMG was robust for negative pressure (R(2) = 0.98) and less strong for other variables such as flow and resistance. These data suggest that independent of central pattern generator activity, intrapharyngeal negative pressure itself modulates genioglossus activity both within breaths and between breaths.     

血脂水平对胰岛功能的影响在2型糖尿病和正常人群中存在差异

研究血脂对胰岛功能的影响在2型糖尿病及正常人群中是否表现不同。结果表明,在正常人群中,处置指数(DI)0与高密度脂蛋白胆固醇(HDL-C)呈正相关,DI30与总胆固醇( TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)呈负相关,DI120与 TC、LDL-C 呈负相关;在2型糖尿病中,DI0与 TC、LDL-C 呈负相关,DI30与 TC、TG、LDL-C、TG/ HDL-C 呈负相关,DI120与 TC、TG、LDL-C、TG/ HDL-C 呈负相关。     

Metabolic effects of inhaled fenoterol in normal subjects.

Although the hypokalemic effect of inhaled beta 2-adrenergic agonists has been well documented, little is known as to their effect on plasma magnesium. We therefore examined in ten healthy young volunteers the effect of the inhalation of 2 mg of nebulized fenoterol on plasma potassium (Kpl), plasma magnesium (Mgpl), and intraerythrocytic magnesium (MgIE) levels, as well as on plasma insulin and C peptide concentrations, measured before and serially up to 110 min after fenoterol inhalation. In all subjects, fenoterol inhalation caused a reversible reduction in Kpl (range, 0.2 to 1.1 mEq/L), which was progressive, reaching a statistically significant nadir 30 to 60 min following fenoterol inhalation (largest dip in Kpl, 0.55 +/- 0.29 mEq/L; p < 0.05). The nadir in Kpl levels was preceded by a peak in plasma insulin levels in all subjects. No significant changes in Mgpl or MgIE were observed in any of the subjects. We conclude that fenoterol inhaled at a dosage used in clinical practice significantly reduces Kpl but not Mgpl nor MgIE levels in healthy subjects, indicating a lower sensitivity of Mg++ ions to beta 2-adrenergic stimulation than K+ ions. Beta 2-adrenergic-induced insulin secretion probably contributes to the hypokalemic effect of inhaled fenoterol.