The duration of intermittent access to preferred sucrose-rich food affects binge-like intake, fat accumulation, and fasting glucose in male rats.

Many people restrict their palatable food intake. In animal models, time-limiting access to palatable foods increases their intake while decreasing intake of less preferred alternatives; negative emotional withdrawal-like behavior is sometimes reported. In drug addiction models, intermittent extended access drives greater changes in use than brief access. When it comes to palatable food, the impact of briefer vs. longer access durations within intermittent access conditions remains unclear. Here, we provided male rats with chow or with weekday access to a preferred, sucrose-rich diet (PREF) (2, 4, or 8 h daily) with chow otherwise available. Despite normal energy intake, all restricted access conditions increased weight gain by 6 weeks and shifted diet acceptance within 1 week. They increased daily and 2-h intake of PREF with individual vulnerability and decreased chow intake. Rats with the briefest access had the greatest binge-like (2-h) intake, did not lose weight on weekends despite undereating chow, and were fattier by 12 weeks. Extended access rats (8 h) showed the greatest daily intake of preferred food and corresponding undereating of chow, slower weight gain when PREF was unavailable, and more variable daily energy intake from week to week. Increased fasting glucose was seen in 2-h and 8-h access rats. During acute withdrawal from PREF to chow diet, restricted access rats showed increased locomotor activity. Thus, intermittent access broadly promoted weight gain, fasting hyperglycemia and psychomotor arousal during early withdrawal. More restricted access promoted greater binge-like intake and fat accumulation, whereas longer access promoted evidence of greater food reward tolerance.

Prospective study of microalbuminuria as predictor of mortality in NIDDM.

Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the predictive power of microalbuminuria is independent of other major cardiovascular risk factors. During 1985-1987, we examined a representative group of 141 nonproteinuric patients with NIDDM for the prevalence of coronary heart disease and several of its established and putative risk factors, including raised urinary albumin excretion (UAE) rate. Thirty-six patients had microalbuminuria (UAE 20-200 micrograms/min), and 105 had normal UAE (less than 20 micrograms/min). At follow-up, an average of 3.4 yr later, 14 patients had died. There was a highly significant excess mortality (chiefly from cardiovascular disease) among those with microalbuminuria (28%) compared to those without microalbuminuria (4%, P less than 0.001). In univariate survival analysis, significant predictors of all-cause mortality included microalbuminuria (P less than 0.001), hypercholesterolemia (P less than 0.01), hypertriglyceridemia (P less than 0.05), and preexisting coronary heart disease (P less than 0.05). The predictive power of microalbuminuria persisted after adjustment for the effects of other major risk factors (P less than 0.05). We conclude that microalbuminuria is a significant risk marker for mortality in NIDDM, independent of the other risk factors examined. Its presence can be regarded as an index of increased cardiovascular vulnerability and a signal for vigorous efforts at correction of known risk factors.

Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients.

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria and coronary heart disease in NIDDM: an incidence study.

In most survival studies in NIDDM, microalbuminuria (urinary albumin excretion rate 20-200 microg/min) predicts early mortality; in cross-sectional studies, it is associated with coronary heart disease (CHD) morbidity. It is unclear, however, whether microalbuminuria is a risk factor for the development of CHD or the result of it, and little is known of the factors that predispose to the development of microalbuminuria in NIDDM. We examined these issues in a 7-year prospective study of a hospital-based cohort comprising 146 white NIDDM patients without clinical albuminuria. Microalbuminuria was a significant risk factor for both all-cause mortality (relative risk 3.94, 95% CI 2.04-7.62) and CHD mortality (relative risk 7.40, 95% CI 2.94-18.7) when adjusted for age only. Its independent predictive power did not persist, however, in age-adjusted multivariable survival analysis that allowed for the other significant risk factors: male sex, preexisting CHD, high levels of glycated hemoglobin, and high serum cholesterol. Among men free of CHD at baseline, the independent risk factors for CHD morbidity and mortality were microalbuminuria, current smoking, high diastolic blood pressure, and high serum cholesterol (all P < 0.05). For the 100 NIDDM patients with normoalbuminuria at baseline, the incidence of microalbuminuria was 29% over the 7-year period. In that group, fasting plasma glucose, current smoking, preexisting CHD, and high initial urinary albumin excretion rate were risk factors for the development of microalbuminuria (all P < 0.05). When men and women were analyzed separately, preexisting CHD was a significant risk factor in men only. These results demonstrate that microalbuminuria predicts incident clinical CHD in men with NIDDM. Preexisting CHD is also a risk factor for incident microalbuminuria in men, however, suggesting that microalbuminuria and CHD are not causally related but rather reflect common determinants.

Systematic review on urine albumin testing for early detection of diabetic complications.

OBJECTIVES: To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure control has a greater influence on the development of diabetic complications in those with microalbuminuria than in those with normoalbuminuria. DATA SOURCES: Electronic databases up until January 2002. REVIEW METHODS: A protocol for peer review by an external expert panel was prepared that included selection criteria for data extraction and required two independent reviewers to undertake article selection and review. Completeness was assessed using hand-searching of major journals. Random effects meta-analysis was used to obtain combined estimates of relative risk (RR). Funnel plots, trim and fill methods and meta-regression were used to assess publication bias and sources of heterogeneity. RESULTS: In patients with type 1 or type 2 DM and microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs were found for other mortality end-points, with age of cohort being inversely related to the RR in type 2 DM. In patients with type 1 DM, there is evidence that microalbuminuria or raised albumin excretion rate has only weak, if any, independent prognostic significance for the incidence of retinopathy and no evidence that it predicts progression of retinopathy, although strong evidence exists for the independent prognostic significance of microalbuminuria or raised albumin excretion rate for the development of proliferative retinopathy (crude RR of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any independent prognostic significance for the incidence of retinopathy and little, if any, prognostic relationship between microalbuminuria and the progression of retinopathy or development of proliferative retinopathy. In patients with type 1 DM and microalbuminuria there is an RR of developing end-stage renal disease (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of developing clinical proteinuria, with a significantly greater fall in glomerular filtration rate (GFR) in patients with microalbuminuria. In patients with type 2 DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and 7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI 0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric. In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers progressing to clinical proteinuria (19% and 24%, respectively) and those regressing to normoalbuminuria (26% and 18%, respectively) did not differ significantly. In children with type 1 DM, regression (44%) was significantly more frequent than progression (15%). In patients with type 1 or type 2 DM and microalbuminuria, there is scarce evidence as to whether improved glycaemic control has any effect on the incidence of cardiovascular disease (CVD), the incidence or progression of retinopathy, or the development of renal complications. However, among patients not stratified by albuminuria, improved glycaemic control benefits retinal and renal complications and may benefit CVD. In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in normotensive microalbuminuric patients with type 1 DM, there was no evidence of a consistent treatment effect. There is strong evidence from 11 trials in normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE inhibitor treatment on the risk of developing clinical proteinuria and on the risk of regression to normoalbuminuria. Patients with type 2 DM and microalbuminuria, whether hypertensive or not, may obtain additional cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect on the development of retinopathy in normotensive patients irrespective of albuminuria. There is limited evidence that treatment of hypertensive microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin system is associated with preserved GFR, but also evidence of no differences in GFR in comparisons with other antihypertensive agents. The data on GFR in normotensive cohorts are inconclusive. In normotensive type 2 patients with microalbuminuria there is evidence from three trials (all enalapril) of a reduction in risk of developing clinical proteinuria; in hypertensive patients there is evidence from one placebo-controlled trial (irbesartan) of a reduction in this risk. Intensive compared with moderate blood pressure control did not affect the rate of progression of microalbuminuria to clinical proteinuria in the one available study. There is inconclusive evidence from four trials of any difference in the proportions of hypertensive patients progressing from microalbuminuria to clinical proteinuria when ACE inhibitors are compared with other antihypertensive agents, and in one trial regression was two-fold higher with lisinopril than with nifedipine. CONCLUSIONS: The most pronounced benefits of glycaemic control identified in this review are on retinal and renal complications in both normoalbuminuric and microalbuminuric patients considered together, with little or no evidence of any greater benefit in those with microalbuminuria. Hence, microalbuminuric status may be a false boundary when considering the benefits of glycaemic control. Classification of a person as normoalbuminuric must not serve to suggest that they will derive less benefit from optimal glycaemic control than a person who is microalbuminuric. All hypertensive patients benefit from blood pressure lowering and there is little evidence of additional benefit in those with microalbuminuria. Antihypertensive therapy with an ACE inhibitor in normotensive patients with microalbuminuria is beneficial. Monitoring microalbuminuria does not have a proven role in modulating antihypertensive therapy while the patient remains hypertensive. Recommendations for microalbuminuria research include: determining rate and predictors of development and factors involved in regression; carrying out economic evaluations of different screening strategies; investigating the effects of screening on patients; standardising screening tests to enable use of common reference ranges; evaluating the effects of lipid-lowering therapy; and using to modulate antihypertensive therapy.

Ethnic differences in correlates of microalbuminuria in NIDDM. The role of the acute-phase response.

OBJECTIVE: To investigate whether microalbuminuria is associated with markers of the acute-phase response in NIDDM and whether there are ethnic differences in this association among the three main racial groups in Malaysia. RESEARCH DESIGN AND METHODS: NIDDM patients of Chinese, Indian, and Malay origin attending a diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes duration, and glycemic control (n = 34 in each group). Urinary albumin-to-creatinine ratio was measured in an early morning urine sample. Biochemical measurements included markers of the acute-phase response: serum sialic acid, triglyceride, and (lowered) HDL cholesterol. RESULTS: The frequency of microalbuminuria did not differ among the Chinese, Indian, and Malay patients (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria had evidence of an augmented acute-phase response, with higher serum sialic acid and triglyceride and lower HDL cholesterol levels; and urinary albumin-to-creatinine ratio was correlated with serum sialic acid and triglyceride. The acute-phase response markers were not different in Indians, with microalbuminuria being high in even the normoalbuminuric Indians; only the mean arterial blood pressure was correlated with urinary albumin-to-creatinine ratio in the Indians. Malay NIDDM subjects had an association of microalbuminuria with acute-phase markers, but this was weaker than in the Chinese subjects. CONCLUSIONS: Microalbuminuria is associated with an acute-phase response in Chinese NIDDM patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated urinary albumin excretion has different correlates in other racial groups, such as those originating from the Indian subcontinent. The acute-phase response may have an etiological role in microalbuminuria.

Serum sialic acid concentration and coronary heart disease in NIDDM.

OBJECTIVE--To examine the association between serum sialic acid concentrations and coronary heart disease (CHD) in a cross-sectional study of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--NIDDM patients (n = 145) attending a diabetic clinic were studied. CHD status was assessed by questionnaire and electrocardiogram coding, and potential risk factor assessment included measurement of fasting serum lipid and lipoprotein concentrations, blood pressure, and urinary albumin excretion rate (AER). RESULTS--Male NIDDM patients with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24, 2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence interval). They were also older, had a longer duration of diabetes, had a higher AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1 concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia, and hypertension were associated with CHD. In women, only hypertension treatment was associated with CHD. CONCLUSIONS--There is a strong univariate association between elevated serum sialic acid and CHD in men (but not women) with NIDDM.

Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group.

OBJECTIVE: To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS: The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean +/- SD duration of diabetes was 14.7 +/- 9.3 years. RESULTS: The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15-29 years old to 25% in patients 45-59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS: The overall prevalence of CVD in these IDDM patients was approximately 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Biosynthetic human insulin: effect in healthy men on plasma glucose and non-esterified fatty acids in comparison with highly purified pork insulin.

Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.

Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients.

A familial predisposition to arterial hypertension has recently been suggested as one important component of the susceptibility to diabetic kidney disease. Sodium-lithium countertransport activity, a marker of risk for essential hypertension, has been found to be increased in diabetic patients with overt nephropathy. We have measured red blood cell sodium-lithium counter-transport activity in 36 microalbuminuric insulin-dependent diabetic patients, a group at high risk of progression to clinical nephropathy and cardiovascular disease, and compared it with that of a matched group of 36 normoalbuminuric diabetic patients. Sodium-lithium countertransport was higher in the microalbuminuric (0.43 [95% confidence interval (CI) 0.38-0.47] mmol/l red blood cells [RBC]/hr) than in the normoalbuminuric diabetic patients (0.29 [0.25-0.33] mmol/l RBC/hr, mean difference 0.14 [0.08-0.20]; p less than 0.0001). Microalbuminuric patients had a higher frequency of parental hypertension than normoalbuminuric diabetic patients (56% vs. 28%, p less than 0.05). Sodium-lithium countertransport was related to mean arterial pressure in the microalbuminuric patients (r = 0.54, p less than 0.001) and to daily insulin requirements in both groups (microalbuminuric patients r = 0.39, p less than 0.05; normoalbuminuric patients r = 0.42, p less than 0.01). In a subset of patients in whom lipoproteins were measured, sodium-lithium countertransport activity was related to total and very low density lipoprotein triglycerides (r = 0.41, p less than 0.05 and r = 0.48, p less than 0.05) and to apolipoprotein B (r = 0.56, p less than 0.05), independently of body mass index, albumin excretion rate, glycemic control, and insulin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoproteins and plasma cholesterol esterification in normal and diabetic subjects.

Serum lipoproteins, separated by preparative ultracentrifugation and the activity of the plasma enzyme lecithin: cholesterol acyltransferase (LCAT) have been measured in insulin-dependent diabetics, non-insulin-dependent diabetics and in age-matched non-diabetic controls. In the insulin-dependent diabetics, mean total serum cholesterol and high density lipoprotein cholesterol (HDL-C) concentrations were significantly higher than in controls. Non-insulin-dependent diabetics had significantly raised total triglycerides and cholesterol, but HDL-C levels were essentially normal. The increased low density lipoprotein cholesterol (LDL-C) in both diabetic groups was statistically significant in men. A methodological study of HDL separation techniques was carried out to facilitate interpretation of these findings. Mean LCAT activity, by a method reflecting combined enzyme and substrate effects was significantly increased in these diabetic groups. The results confirm recent reports of a raised HDL-C in those insulin-dependent diabetics who are prone to coronary heart disease.

High density lipoprotein subfractions in insulin-dependent diabetic and normal subjects.

Serum lipoproteins have been separated by preparative ultracentrifugation in randomly selected groups of insulin-dependent diabetics and in age- and sex-matched non-diabetic controls. The major high density lipoprotein (HDL) subclass; HDL2 (density (d) 1.063-1.125 kg X m-3) and HDL3 (d greater than 1.125) and the further fractions of HDL2:HDL2b (d 1.063-1.100) and HDL2a (d 1.100-1.125) were also separated and their cholesterol (C) concentrations determined. These diabetic men and women were relatively normolipaemic and the major difference from controls was a significantly raised total HDL-C in men which was confirmed by a separate chemical precipitation method. This increase was associated with a significant rise in HDL2a-C and in total HDL2-C concentration. The non-significant increase in diabetic women compared to men was associated with poorer metabolic control. Among factors influencing serum HDL2-C concentration, the most important was the negative association with the level of very low density lipoprotein-triglycerides. Although insulin-dependent diabetics have an increased risk of atherosclerotic coronary heart disease (CHD), this is not reflected in their HDL subfraction-C distribution which, if present in non-diabetics, would be expected to confer protection from CHD.

The relationship of high density lipoprotein subfractions to alcohol consumption, other lifestyle factors, and coronary heart disease.

Serum high density lipoprotein (HDL) levels are inversely related to the risk of coronary heart disease. Controversy exists regarding the relative importance of HDL subfractions, and few studies have related subfraction levels to lifestyle factors associated with coronary risk. We examined the relationship of the major subfractions, HDL2 and HDL3, to alcohol consumption, cigarette smoking, physical exercise, body mass index, and socioeconomic status in 88 men and 49 women aged 35-64 years. Body mass index was inversely related to HDL2-cholesterol (C), particularly in men, but had no significant relationship with HDL3-C. Cigarette smoking and degree of physical exercise were not significantly related to either HDL subfraction. Alcohol consumption had a strong positive correlation with HDL3-C in both sexes; this association was statistically significant after controlling for cigarette smoking, body mass index, and serum triglyceride. Minnesota-coded ECG abnormalities and positive responses to the WHO chest pain questionnaire were associated with lower levels of HDL-C and HDL2-C in both sexes, and significantly lowered levels of HDL3-C in men but not women. These findings suggest that HDL3-C, as well as HDL2-C, may be related to coronary risk, and indicate that the protective effects of alcohol consumption may be mediated via this subfraction.

Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis.

Recorded deaths from coronary and cerebral thrombosis rise markedly in heat waves. In a British heat wave with little or no distortion due to air-conditioning, outside temperatures of 34.6 degrees C (maximum) and 20.8 degrees C (minimum) were followed by peak mortalities from coronary and cerebral thrombosis one to two days later. Experimental exposure of volunteers to moving air at 41 degrees C for six hours caused core temperature to rise 0.84 degree C, weight to fall 1.83 kg with sweating despite access to water, heart rate to increase 32 beats per minute, and arterial pressure to fall, particularly on standing. The red blood cell count increased 9 percent, and blood viscosity increased 24 percent, mostly after the first hour. The platelet count rose 18 percent, and the platelet volume fell, mostly in the first hour. The plasma cholesterol level increased 14 percent without a change in distribution among lipoprotein fractions. The changes seem able to explain the increased mortality from arterial thrombosis in hot weather.

Mechanism of carbohydrate-induced hypertriglyceridemia: plasma lipid metabolism in mice.

A group of mice were fed on a basal diet for 2 wk and thereafter maintained on a fat free high sucrose or starch diet for 5-6 wk. Hypertriglyceridemia was induced in the mice on feeding the high carbohydrate diets. The triglyceride levels reached maximum in 12 and 14-18 days on high sucrose and starch diets, respectively. This was associated with increased pre-beta-lipoproteins in plasma. Though males had higher levels of triglycerides than females on both the diets, this attained statistical significance only in the sucrose-fed group. Cholesterol and phospholipids recorded a significant increase only towards the end of the experimental period. The plasma lipid levels correlated with their secretion rates from the liver following an injection of Triton WR 1339. Furthermore, the hypertriglyceridemia appeared to be due to defective plasma triglyceride removal as seen by the reduced postheparin lipolytic activity (PHLA) of plasma and decreased triglyceride removal (intravenous fat tolerance test) in these animals. The triglycerides returned to almost normal levels when feeding was continued on the diets. During this adaptation, PHLA and fat tolerance of animals increased significantly. Higher triglycerides in the sucrose group seem to be due to a higher rate of secretion as well as slower removal of triglycerides in this group. The sex difference noticed in the plasma triglycerides at peak hypertriglyceridemia appeared to be mainly due to sex difference in removal rates. Blood sugar raised significantly in the animals maintained on both the diets.

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE: To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN: Case-control study. SETTING: Outpatient department of a metabolic ward. PATIENTS: Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS: Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT: Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS: Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS: Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.